Dopamine's Central Role in the Brain's Motivation and Reward Networks:
Researchers use two imaging methods to pinpoint dopamine as key chemical in human brain's pleasure and motivation circuits
Researchers have for the first time found that the neurotransmitter dopamine is central to the human brain network governing motivation and a sense of reward and pleasure—and that it changes with age. The finding could provide clues to healthy, happy aging and pave the way to new treatments for neurological disorders, including Parkinson's disease and schizophrenia as well as addictive behaviors from alcoholism and drug abuse to compulsive gambling.
The U.S. National Institute of Mental Health (NIMH) team used two imaging methods, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), to examine the normal human brain reward circuit, a complex neurochemical network that centers around a path from the ventral tegmental area in the midbrain (where dopamine is synthesized) to the nucleus accumbens in the forebrain (where it is released). Comparing brain activity in volunteers playing video slot machines, the researchers identified processes involved both in anticipating a reward and actually getting one—and discerned age-dependent changes in those processes.
Wolfram Schultz, a neuroscientist at the University of Cambridge in England, says the researchers "have tried to push the frontier" by combining two imaging techniques: fMRI, which measures time course, and the PET study, which measures dopamine synthesis rate. "This is a very smart combination," he says.
The study, published today in the Proceedings of the National Academy of Sciences USA, compared brain activity in 20 younger subjects (mean age 25) with that in 13 older ones (mean age 66), all in good health. "This is building a foundation upon which we can search for interventions when aging is not so successful or when this reward system is abnormal," says senior study author Karen Berman, chief of the integrative neuroimaging at NIMH's Clinical Brain Disorders Branch. Bruce Jenkins, director of neurochemical imaging at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital in Boston, praised the study, although he noted the small number of subjects. The next step, he said, should be to investigate the mechanism underlying the age-related changes.
On tap: similar studies of people whose aging has not been successful or who suffer from dopamine-related states such as Parkinson's, depression and addictions. Berman says she and her NIMH colleagues have already launched such a study of schizophrenia, a disorder characterized both by hallucinations and loss of motivation. The malady has long been known to involve dopamine circuits.
Source: Scientific American, Tabitha Powledge
Yin And Yang
Balance
Thursday, October 29, 2009
Wednesday, October 28, 2009
Psychiatric Disorder
Dopamine Pathway Alterations May Be Associated With Symptoms of Adult ADHD
Read more September 11, 2009 Preliminary results from a new imaging study suggest that there is an association between a reduction in the transmission of dopamine in the brain and symptoms of attention deficit hyperactivity disorder (ADHD) in adults.
"This study provides evidence in favor of the predicted disruption in the mesoaccumbens dopamine pathway in ADHD," write Nora D. Volkow, MD, director of the National Institute on Drug Abuse and Laboratory of Neuroimaging at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, and colleagues.
In addition to finding lower postsynaptic D2/D3 receptor markers and lower presynaptic dopamine transporter (DAT) markers in those with ADHD, compared with a group of control patients, in 2 key brain regions for reward and motivation (accumbens and midbrain), the study also corroborated disruption of synaptic dopamine markers in the caudate region and provided preliminary evidence of hypothalamic involvement.
"Basically, this study showed that individuals with ADHD have a significant decrease in both of these markers in the dopamine areas associated with reward, motivation, and drive," Dr. Volkow told Medscape Psychiatry
"We also showed that the decreases in these markers were associated with the severity of inattention. In other words, the lower the concentration of these markers in these areas of the dopamine reward pathway, the more intense the symptoms of inattention," she added.
The study was published in the September 9 issue of JAMA.
Evaluating Biological Bases
ADHD is the most prevalent childhood psychiatric disorder that persists into adulthood, affecting about 3% to 5% of the US adult population, report the authors.
Evidence from previous brain imaging studies has shown that dopamine (a neurotransmitter essential for the normal functioning of the central nervous system) transmission is disrupted in some pathways of the brain in ADHD; these deficits may underlie core symptoms of inattention and impulsivity.
In addition, there is also increased awareness that patients with ADHD may have reward and motivation deficits, typically characterized by abnormal behavior change following conditions of reward and punishment.
After they hypothesized abnormalities in the mesoaccumbens dopamine pathway (composed of dopamine cells in the midbrain and their projections to the accumbens), the investigators sought to evaluate biological bases that might underlie a reward/motivation deficit by imaging key components of this dopamine reward pathway in patients with ADHD.
For this study, Dr. Volkow and her team used positron emission tomography to measure both DAT and D2/D3 receptor markers in 53 nonmedicated adults with ADHD (mean age, 32 years; 51% men) and in 44 control participants without ADHD (mean age, 31 years; 68% men) between 2001 and 2009.
The investigators measured specific binding of positron emission tomography radioligands for DATs using [11C]cocaine, and for D2/D3 receptors using [11C]raclopride, quantified as binding potential (distribution volume ratio, −1). ADHD items were assessed using the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN) rating scale.
For both ligands, statistical parametric mapping at the end of the study showed that specific binding was lower for those with ADHD than in the control participants (threshold for significance set at P < .005) in regions of the dopamine reward pathway in the left side of the brain.
For the D2/D3 receptors, this included the ventral caudate, accumbens, and midbrain regions, as well as the hypothalamic region (HR). "The fact that there was also a dopamine deficit in hypothalamic regions was surprising and not one we searched out," Dr. Volkow explained. "In the past, clinicians have noted that ADHD subjects are more likely to experience 3 symptoms that are consistent with hypothalamic pathology: obesity, sleep disturbances, and reactivity to stress. But this was a totally unexpected finding and not a priority hypothesis. Still, it is very preliminary and in need of replication."
DAT availability was also significantly lower in those with ADHD than those in the control group in the accumbens and midbrain region.
ADHD is a Real Psychiatric Disorder
"The lower than normal D2/D3 receptor and DAT availability in the accumbens and midbrain regions supports the hypothesis of an impairment of the dopamine reward pathway in ADHD," write the study authors.
"Classically, ADHD has been thought of as a disorder where the main problem relates to the attention network," reported Dr. Volkow. "But in this imaging study, we are showing that the main deficit relates to reward pathways that are crucial for engaging attention networks. The primary deficit is not on the personal network but on the system that is required to engage it. For example, your car may work very well. But if you have no gasoline, you can not engage the engine."
She added that these findings support the need for interventions to enhance the saliency of school and work tasks to improve performance in those with ADHD.
In addition, there has been an enormous amount of conflict and debate about whether ADHD is really a disorder or just a behavioral disruption that emerges as a function of a poor education or curriculum. "By being able to clearly show biochemical and functional changes in the brain of individuals with ADHD, this study helps with the recognition of ADHD as a real psychiatric disorder," she added.
The next step for the investigative team is a study examining how genetics generate dopamine reward pathways. "We'll be asking how genetics affect the wiring of the brain, resulting in some people having these deficits and others not," Dr. Volkow concluded.
Source: JAMA
*This study was supported in part by a grant from the Intramural Research Program of the National Institutes of Health and by the National Institute of Mental Health.
Read more September 11, 2009 Preliminary results from a new imaging study suggest that there is an association between a reduction in the transmission of dopamine in the brain and symptoms of attention deficit hyperactivity disorder (ADHD) in adults.
"This study provides evidence in favor of the predicted disruption in the mesoaccumbens dopamine pathway in ADHD," write Nora D. Volkow, MD, director of the National Institute on Drug Abuse and Laboratory of Neuroimaging at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, and colleagues.
In addition to finding lower postsynaptic D2/D3 receptor markers and lower presynaptic dopamine transporter (DAT) markers in those with ADHD, compared with a group of control patients, in 2 key brain regions for reward and motivation (accumbens and midbrain), the study also corroborated disruption of synaptic dopamine markers in the caudate region and provided preliminary evidence of hypothalamic involvement.
"Basically, this study showed that individuals with ADHD have a significant decrease in both of these markers in the dopamine areas associated with reward, motivation, and drive," Dr. Volkow told Medscape Psychiatry
"We also showed that the decreases in these markers were associated with the severity of inattention. In other words, the lower the concentration of these markers in these areas of the dopamine reward pathway, the more intense the symptoms of inattention," she added.
The study was published in the September 9 issue of JAMA.
Evaluating Biological Bases
ADHD is the most prevalent childhood psychiatric disorder that persists into adulthood, affecting about 3% to 5% of the US adult population, report the authors.
Evidence from previous brain imaging studies has shown that dopamine (a neurotransmitter essential for the normal functioning of the central nervous system) transmission is disrupted in some pathways of the brain in ADHD; these deficits may underlie core symptoms of inattention and impulsivity.
In addition, there is also increased awareness that patients with ADHD may have reward and motivation deficits, typically characterized by abnormal behavior change following conditions of reward and punishment.
After they hypothesized abnormalities in the mesoaccumbens dopamine pathway (composed of dopamine cells in the midbrain and their projections to the accumbens), the investigators sought to evaluate biological bases that might underlie a reward/motivation deficit by imaging key components of this dopamine reward pathway in patients with ADHD.
For this study, Dr. Volkow and her team used positron emission tomography to measure both DAT and D2/D3 receptor markers in 53 nonmedicated adults with ADHD (mean age, 32 years; 51% men) and in 44 control participants without ADHD (mean age, 31 years; 68% men) between 2001 and 2009.
The investigators measured specific binding of positron emission tomography radioligands for DATs using [11C]cocaine, and for D2/D3 receptors using [11C]raclopride, quantified as binding potential (distribution volume ratio, −1). ADHD items were assessed using the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN) rating scale.
For both ligands, statistical parametric mapping at the end of the study showed that specific binding was lower for those with ADHD than in the control participants (threshold for significance set at P < .005) in regions of the dopamine reward pathway in the left side of the brain.
For the D2/D3 receptors, this included the ventral caudate, accumbens, and midbrain regions, as well as the hypothalamic region (HR). "The fact that there was also a dopamine deficit in hypothalamic regions was surprising and not one we searched out," Dr. Volkow explained. "In the past, clinicians have noted that ADHD subjects are more likely to experience 3 symptoms that are consistent with hypothalamic pathology: obesity, sleep disturbances, and reactivity to stress. But this was a totally unexpected finding and not a priority hypothesis. Still, it is very preliminary and in need of replication."
DAT availability was also significantly lower in those with ADHD than those in the control group in the accumbens and midbrain region.
ADHD is a Real Psychiatric Disorder
"The lower than normal D2/D3 receptor and DAT availability in the accumbens and midbrain regions supports the hypothesis of an impairment of the dopamine reward pathway in ADHD," write the study authors.
"Classically, ADHD has been thought of as a disorder where the main problem relates to the attention network," reported Dr. Volkow. "But in this imaging study, we are showing that the main deficit relates to reward pathways that are crucial for engaging attention networks. The primary deficit is not on the personal network but on the system that is required to engage it. For example, your car may work very well. But if you have no gasoline, you can not engage the engine."
She added that these findings support the need for interventions to enhance the saliency of school and work tasks to improve performance in those with ADHD.
In addition, there has been an enormous amount of conflict and debate about whether ADHD is really a disorder or just a behavioral disruption that emerges as a function of a poor education or curriculum. "By being able to clearly show biochemical and functional changes in the brain of individuals with ADHD, this study helps with the recognition of ADHD as a real psychiatric disorder," she added.
The next step for the investigative team is a study examining how genetics generate dopamine reward pathways. "We'll be asking how genetics affect the wiring of the brain, resulting in some people having these deficits and others not," Dr. Volkow concluded.
Source: JAMA
*This study was supported in part by a grant from the Intramural Research Program of the National Institutes of Health and by the National Institute of Mental Health.
Deprenyl Improves Learning And Memory
Several animal studies have shown that both deprenyl (and its metabolite 1-amphetamine) improves learning and memory. In one study at the University of Saskatchewan in Canada, both young (2-month old) and middle- aged (10-month old) male Wister rats were tested on a modified Morris Water Maze. Every animal went through ten trials a day for five consecutive days.30
The middle-aged deprenyl-treated animals learned the maze in an average of only 11 trials compared to 19 trials for the control animals. The middle-aged deprenyl rats even did better than the young controls, who took an average of 13 trials to learn the maze.
Dopamine is one of the most important substances in the brain. It is an essential neurotransmitter that regulates movement, coordination, sex drive, and other critical functions. The lack of it causes Parkinson's Disease, which leads to disability, cognitive decline, and death.
Source:
LE Magazine September
The middle-aged deprenyl-treated animals learned the maze in an average of only 11 trials compared to 19 trials for the control animals. The middle-aged deprenyl rats even did better than the young controls, who took an average of 13 trials to learn the maze.
Dopamine is one of the most important substances in the brain. It is an essential neurotransmitter that regulates movement, coordination, sex drive, and other critical functions. The lack of it causes Parkinson's Disease, which leads to disability, cognitive decline, and death.
Source:
LE Magazine September
Extending the Maximum Life Span:
Joseph Knoll, M.D., is a Hungarian neurochemist and pharmacologist. He is probably best known for developing the drug deprenyl (also known as Selegiline), the first selective MAO-B inhibitor, and he has researched the properties of deprenyl for over half a century.
MAO is Monoa-mine Oxidase, an enzyme in the brain that breaks down neurotransmitters. By inhibiting the production of MAO, you increase the longevity of neurotransmitters in the synapses between neurons, and, consequently, the effects of those neurotransmitters. MAO-B is specific to break down the excitatory neurotransmitter dopamine. So by inhibiting MAO-B, you enhance the effects of dopamine in the brain.
Dr. Knoll is also the author of the book The Brain and Its Self: A Neurochemical Concept of Innate and Acquired Drives (Springer, 2005), which summarizes his life's research and his fascinating speculations about the relationship between brain activity and culture.
In this book, Dr. Knoll describes how his experience as a Nazi concentration camp survivor helped to inspire and motivate much of his scientific research. Although his parents were sent to the gas chamber when he was a teenager, Dr. Knoll survived because he spoke fluent German and was chosen to serve as the personal servant to the Chief of the SS guards. In 1945, after the war, Dr. Knoll returned to his native city of Budapest. He earned his M.D. from the University of Budapest in 1951, and later became a professor and the head of the Department of Pharmacology at the Semmelweiss University of Medicine in Budapest.
In the early 1950s, Dr. Knoll helped to pioneer research into the physiological basis of innate and acquired drives in animals. Trying to make sense of his experience in the Nazi concentration camp, he became interested in how animals acquire new drives. The research that resulted from his interest in this subject centered around studying the brain changes in rats that had been trained to have an acquired drive for an unnatural object—a glass cylinder.
This acquired drive—which urged the animals to search for, and jump to, the rim of a thirty centimeter-high glass-cylinder, and then crawl inside—would often override the animals' instinctive drives for food and sex.
Dr. Knoll first synthesized deprenyl in his Budapest laboratory in 1961 and showed that deprenyl improves the availability of dopamine, and slows its age-related decline by acting as a selective MAO-B inhibitor. As well, it has an enhancer effect, and it helps maintain healthy brain cells, particularly in the dopamine-producing area of the brain known as the substantia nigra—the area of the brain that degenerates with Parkinson's Disease. For this reason deprenyl has been used as an effective treatment for Parkinson's Disease. It has also been shown to be an effective treatment for Alzheimer's Disease and other brain disorders that result in cognitive decline.
Deprenyl has been shown to have many uses as a cognitive enhancer. It is a moderate-level stimulant and antidepressant that has been shown to improve memory, protect the brain against cell damage, alleviate depression, extend the life span of laboratory animals, and heighten sexual desire in both men and women. This impressive substance is available by prescription in the U.S., and although it is primarily prescribed to help people with Parkinson's disease, memory disorder problems, and sometimes depression, a lot of healthy people also use deprenyl to improve their mental performance. In fact, Dr. Knoll himself takes deprenyl every day, and recommends that every sexually mature person should be doing the same.
Along with other cognitive enhancers, such as hydergine and piracetam, I think that deprenyl has incredible potential for enhancing memory, accelerating intelligence, and improving concentration. There is a good deal of scientific evidence to support these claims. Find a summary of the scientific studies in this area in John Morgenthaler and Ward Dean's book Smart Drugs and Nutrients II.
Many people report that deprenyl and other "smart drugs" have sexually-enhancing "side-effects," although deprenyl appears to have the leading reputation in this area. According to Dr. Dean—the coauthor of Smart Drugs and Nutrients—"anything that improves brain function is probably going to improve sexual functioning." This is probably because sexuality and health go hand-in-hand, and sexual vitality is a pretty good indicator of overall health.
Dr. Knoll and colleagues first reported indications for deprenyl's potential as a sexuality enhancer in 1983, with reports that old male rats had increased their "mounting frequency" and "intromission" when they were treated with deprenyl. This contrasted dramatically with the untreated control animals. Many anecdotal reports, from both men and women, have confirmed that these aphrodisiac-like effects apply to humans as well. Because deprenyl inhibits MAO—the dopamine-destroying enzyme—levels of the excitatory neurotransmitter dopamine rise in the brain, which generally causes people to feel more pleasure and become more physiologically aroused.
Interestingly, unlike most other MAO inhibitor drugs (such as the antidepressant Nardil), there are usually no dietary restrictions necessary when one takes deprenyl. When taken at moderate levels (under 10 mg), deprenyl only inhibits the action of a specific type of MAO—MAO B—which doesn't interfere with the body's ability to metabolize the dietary amine tyramine, like a broad-spectrum MAO inhibitor does. This is why most other MAO-inhibiting drugs carry the serious danger of triggering a hypertensive reaction if one eats tyramine-rich foods, like cheese or wine. Deprenyl has been described by researchers as working with great precision in this regard, and the physicians that I spoke with agreed that it was unusually safe.
In fact, deprenyl is better than safe. This truly remarkable drug has also been shown to increase the maximum lifespan of laboratory animals by close to forty percent. This is the equivalent of a human being living to be around one hundred fifty years of age. Giving deprenyl to animals is the only experimental treatment—besides caloric restriction—that has been shown to increase maximum life span.
To fully appreciate how significant deprenyl's life extension potential is, one has to understand the difference between maximum life span and average life span. Many factors can affect the average lifespan (or the "normal life expectancy") that an animal lives—genetics, diet, exercise, nutritional supplements, mental attitude, etc. However, even under the very best of conditions, there is an upper limit at which the longest-lived animals of a particular species can survive, and that is the animal's maximum life span.
The average life span of a human being is approximately seventy to eighty years. However, the maximum life span of a human being is around one hundred twenty years. The laboratory animals in the deprenyl studies showed a forty percent increase in maximum life span, the human equivalent of living one hundred fifty years. Since deprenyl's primary effects work the same in all mammalian brains, it stands to reason that deprenyl's life extension effects are likely to carry over to humans, just as the mental benefits do. Many people have certainly verified that the increase in sex drive occurs in both humans and laboratory animals.
How people can utilize deprenyl for its cognitive enhancing and anti-aging benefits, and what type of anti-aging treatments might be available in the future.
As a survivor of Auschwitz, and one of the 1,300 survivors of the "Dachau Death Train," I had the opportunity to directly experience a few typical representatives of this type of manipulated human beings, and had more than enough time and direct experience to reflect upon the essential changes in the physiological manipulability of the human brain. It was therefore not just by mere chance that, when in the early 1950s I finally had the opportunity to approach this problem experimentally, I decided to develop a rat model to follow the changes in the brain in the course of the acquisition of a drive from the start of training until its manifestation.
Successful clinical studies with deprenyl were executed in depression and in the two age-related neurodegenerative diseases: Parkinson's Disease and Alzheimer's Disease. The first clinical study performed in depressed patients by Dr. Varga with deprenyl was published in 1965. The clinical use of deprenyl in Parkinson's Disease started in 1977. The first two papers demonstrating the effectiveness of deprenyl in Alzheimer's Disease appeared in 1987. Deprenyl was originally developed with the intention to be used as a new spectrum antidepressant. Its effectiveness was first demonstrated with the racemic form of the compound by Dr. Varga and his coworkers in 1965 and 1967, and with the enantiomer in 1971. The first study that corroborated the antidepressant effect of deprenyl was published by Dr. Mann and Dr. Gershon in 1980.
The realization of the peculiar effect of deprenyl—first in Parkinson's Disease and later in Alzheimer's Disease—distracted attention from its antidepressant property which remains unutilized.
Knoll thinks the primary causes of aging in general is survival of the species. Various species live together on earth in a harmonious proportion. This is obviously carefully regulated. One of the seemingly principal regulatory mechanisms that produces equilibrium among living organisms is brain aging. It ultimately leads to the elimination of those individuals who have already fulfilled their duty in nurturing the new generation.
Accordingly, the period from weaning until sexual maturity is reached is the most delightful phase of life, the glorious uphill journey. The individual progressively takes possession, on a mature level, of all abilities crucial for survival and maintenance of the species. It learns to avoid dangerous situations, masters the techniques to obtain its food, develops procreative powers for sexual reproduction and copulates.
This is, at the same time, the climax of developmental longevity. The fully sexually mature individual fulfills its duty. Thus, to maintain the precisely balanced out natural equilibrium among living organisms, the biologically "useless" individual has to be eliminated. According to the inborn program, the postdevelopmental stage of life (aging) begins. The essence of this stage is progressive decay of the efficiency of the catecholaminergic system during the postdevelopmental life span until at some point, in an emergency situation, the integration of the parts in a highly sophisticated entity can no longer be maintained and "natural death," signaled by the disappearance of the EEG signal, sets in.
Regarding the quality and duration of life, the most important aging process is the continuous, slow, age-related decline of the mesencephalic enhancer regulation during the postdevelopment phase of life. This can not be reversed, but its progress can be slowed by the prophylactic administration of a synthetic mesencephalic enhancer substance (for the time being with the daily administration of one milligram of deprenyl). The earlier this protective treatment starts, the better are the prospects to improve the quality of life in the latter decades, which necessarily goes together with an extension of life span.
The average life span in the most developed countries has already exceeded the eighty year level. This change has come about due to the prevention of premature deaths owing to the development of hygiene, immunology, and chemotherapy. The human technical life span (TLSh), close to one hundred twenty years, has remained, however, unchanged.
In Knoll's view, to extend the human life span beyond the TLSh needs the elaboration of an ultimate technique for the prophylactic, daily small-dose administration of a safe synthetic mesencephalic enhancer substance from sexual maturity until death. The attainable upper limit in the extension of the TLSh is obviously unpredictable at present.
Nevertheless, if brain research could, at some time in the future, achieve just a doubling of the TLSh, this will mean for humans the most significant accomplishment that science has ever achieved, since nothing can be more important for the individual than the quality and duration of his/her life.
In the developed countries the proportion of the aged is high, and the estimated number of individuals over sixty-five will increase to 1.1 billion by 2050. Accordingly, the demand on anti-aging therapy is rapidly increasing. This trend explains the already high-sounding proposals for anti-aging treatments.
Since the brain alone ensures that the mammalian organism works as a purposeful, motivated, goal-directed entity, the age-related changes in the central nervous system are of particular importance. And since the enhancer-sensitive neurons in the brain stem work as the engine of the brain, the slow, continuous, postdevelopmental functional decline of the mesencephalic enhancer regulation is of primary importance in the maintenance of the well-balanced equilibrium among living organisms, because it helps to eliminate the individuals who already fulfilled their duty in nurturing the new generation.
For the time being the prestigious task—the maintenance of the mesencephalic enhancer regulation during the postdevelopmental phase of life on the enhanced level characteristic of developmental longevity—cannot be fully accomplished. However, it is already feasible to modestly slow the age-related decay of the catecholaminergic and trace-aminergic tone in the brain via the prophylactic administration of one milligram of deprenyl daily.
The development of BPAP—a synthetic mesencephalic enhancer substance that is at least a hundred times more potent than deprenyl—is by itself a hint that our present knowledge about the mesencephalic enhancer regulation is in a very early stage. Better understanding of mesencephalic enhancer regulation promises to develop more efficient techniques in the future to slow brain aging and prolong human life beyond the TLSh. This physiologically well-founded, feasible, antiaging therapy is likely to remain a method to continuously improve the quality, and prolong the duration of human life.
Humans cannot change natural laws, but by discovering their mechanisms of action they learn to make use of this knowledge. By conquering gravitation man stepped across his naturally given limit and ultimately landed on the moon. By conquering the age-related decline of the mesencephalic enhancer regulation man might in the future step across also this naturally given limit and extend human life span beyond the TLSh.
Dr. Knoll's ambition is to develop a more efficient compound than deprenyl for slowing the age-related decay of the mesencephalic enhancer regulation, and to detect the envisioned unknown mesencephalic enhancer substances, expected to be several thousand times more active than PEA or tryptamine. Currently we are trying to clarify in more detail the pharmacological spectrum of BPAP—our newly developed, tryptamine-derived, synthetic mesencephalic enhancer substance.
Joseph Knoll, M.D., is a Hungarian neurochemist and pharmacologist. He is probably best known for developing the drug deprenyl (also known as Selegiline), the first selective MAO-B inhibitor, and he has researched the properties of deprenyl for over half a century.
MAO is Monoa-mine Oxidase, an enzyme in the brain that breaks down neurotransmitters. By inhibiting the production of MAO, you increase the longevity of neurotransmitters in the synapses between neurons, and, consequently, the effects of those neurotransmitters. MAO-B is specific to break down the excitatory neurotransmitter dopamine. So by inhibiting MAO-B, you enhance the effects of dopamine in the brain.
Dr. Knoll is also the author of the book The Brain and Its Self: A Neurochemical Concept of Innate and Acquired Drives (Springer, 2005), which summarizes his life's research and his fascinating speculations about the relationship between brain activity and culture.
In this book, Dr. Knoll describes how his experience as a Nazi concentration camp survivor helped to inspire and motivate much of his scientific research. Although his parents were sent to the gas chamber when he was a teenager, Dr. Knoll survived because he spoke fluent German and was chosen to serve as the personal servant to the Chief of the SS guards. In 1945, after the war, Dr. Knoll returned to his native city of Budapest. He earned his M.D. from the University of Budapest in 1951, and later became a professor and the head of the Department of Pharmacology at the Semmelweiss University of Medicine in Budapest.
In the early 1950s, Dr. Knoll helped to pioneer research into the physiological basis of innate and acquired drives in animals. Trying to make sense of his experience in the Nazi concentration camp, he became interested in how animals acquire new drives. The research that resulted from his interest in this subject centered around studying the brain changes in rats that had been trained to have an acquired drive for an unnatural object—a glass cylinder.
This acquired drive—which urged the animals to search for, and jump to, the rim of a thirty centimeter-high glass-cylinder, and then crawl inside—would often override the animals' instinctive drives for food and sex.
Dr. Knoll first synthesized deprenyl in his Budapest laboratory in 1961 and showed that deprenyl improves the availability of dopamine, and slows its age-related decline by acting as a selective MAO-B inhibitor. As well, it has an enhancer effect, and it helps maintain healthy brain cells, particularly in the dopamine-producing area of the brain known as the substantia nigra—the area of the brain that degenerates with Parkinson's Disease. For this reason deprenyl has been used as an effective treatment for Parkinson's Disease. It has also been shown to be an effective treatment for Alzheimer's Disease and other brain disorders that result in cognitive decline.
Deprenyl has been shown to have many uses as a cognitive enhancer. It is a moderate-level stimulant and antidepressant that has been shown to improve memory, protect the brain against cell damage, alleviate depression, extend the life span of laboratory animals, and heighten sexual desire in both men and women. This impressive substance is available by prescription in the U.S., and although it is primarily prescribed to help people with Parkinson's disease, memory disorder problems, and sometimes depression, a lot of healthy people also use deprenyl to improve their mental performance. In fact, Dr. Knoll himself takes deprenyl every day, and recommends that every sexually mature person should be doing the same.
Along with other cognitive enhancers, such as hydergine and piracetam, I think that deprenyl has incredible potential for enhancing memory, accelerating intelligence, and improving concentration. There is a good deal of scientific evidence to support these claims. Find a summary of the scientific studies in this area in John Morgenthaler and Ward Dean's book Smart Drugs and Nutrients II.
Many people report that deprenyl and other "smart drugs" have sexually-enhancing "side-effects," although deprenyl appears to have the leading reputation in this area. According to Dr. Dean—the coauthor of Smart Drugs and Nutrients—"anything that improves brain function is probably going to improve sexual functioning." This is probably because sexuality and health go hand-in-hand, and sexual vitality is a pretty good indicator of overall health.
Dr. Knoll and colleagues first reported indications for deprenyl's potential as a sexuality enhancer in 1983, with reports that old male rats had increased their "mounting frequency" and "intromission" when they were treated with deprenyl. This contrasted dramatically with the untreated control animals. Many anecdotal reports, from both men and women, have confirmed that these aphrodisiac-like effects apply to humans as well. Because deprenyl inhibits MAO—the dopamine-destroying enzyme—levels of the excitatory neurotransmitter dopamine rise in the brain, which generally causes people to feel more pleasure and become more physiologically aroused.
Interestingly, unlike most other MAO inhibitor drugs (such as the antidepressant Nardil), there are usually no dietary restrictions necessary when one takes deprenyl. When taken at moderate levels (under 10 mg), deprenyl only inhibits the action of a specific type of MAO—MAO B—which doesn't interfere with the body's ability to metabolize the dietary amine tyramine, like a broad-spectrum MAO inhibitor does. This is why most other MAO-inhibiting drugs carry the serious danger of triggering a hypertensive reaction if one eats tyramine-rich foods, like cheese or wine. Deprenyl has been described by researchers as working with great precision in this regard, and the physicians that I spoke with agreed that it was unusually safe.
In fact, deprenyl is better than safe. This truly remarkable drug has also been shown to increase the maximum lifespan of laboratory animals by close to forty percent. This is the equivalent of a human being living to be around one hundred fifty years of age. Giving deprenyl to animals is the only experimental treatment—besides caloric restriction—that has been shown to increase maximum life span.
To fully appreciate how significant deprenyl's life extension potential is, one has to understand the difference between maximum life span and average life span. Many factors can affect the average lifespan (or the "normal life expectancy") that an animal lives—genetics, diet, exercise, nutritional supplements, mental attitude, etc. However, even under the very best of conditions, there is an upper limit at which the longest-lived animals of a particular species can survive, and that is the animal's maximum life span.
The average life span of a human being is approximately seventy to eighty years. However, the maximum life span of a human being is around one hundred twenty years. The laboratory animals in the deprenyl studies showed a forty percent increase in maximum life span, the human equivalent of living one hundred fifty years. Since deprenyl's primary effects work the same in all mammalian brains, it stands to reason that deprenyl's life extension effects are likely to carry over to humans, just as the mental benefits do. Many people have certainly verified that the increase in sex drive occurs in both humans and laboratory animals.
How people can utilize deprenyl for its cognitive enhancing and anti-aging benefits, and what type of anti-aging treatments might be available in the future.
As a survivor of Auschwitz, and one of the 1,300 survivors of the "Dachau Death Train," I had the opportunity to directly experience a few typical representatives of this type of manipulated human beings, and had more than enough time and direct experience to reflect upon the essential changes in the physiological manipulability of the human brain. It was therefore not just by mere chance that, when in the early 1950s I finally had the opportunity to approach this problem experimentally, I decided to develop a rat model to follow the changes in the brain in the course of the acquisition of a drive from the start of training until its manifestation.
Successful clinical studies with deprenyl were executed in depression and in the two age-related neurodegenerative diseases: Parkinson's Disease and Alzheimer's Disease. The first clinical study performed in depressed patients by Dr. Varga with deprenyl was published in 1965. The clinical use of deprenyl in Parkinson's Disease started in 1977. The first two papers demonstrating the effectiveness of deprenyl in Alzheimer's Disease appeared in 1987. Deprenyl was originally developed with the intention to be used as a new spectrum antidepressant. Its effectiveness was first demonstrated with the racemic form of the compound by Dr. Varga and his coworkers in 1965 and 1967, and with the enantiomer in 1971. The first study that corroborated the antidepressant effect of deprenyl was published by Dr. Mann and Dr. Gershon in 1980.
The realization of the peculiar effect of deprenyl—first in Parkinson's Disease and later in Alzheimer's Disease—distracted attention from its antidepressant property which remains unutilized.
Knoll thinks the primary causes of aging in general is survival of the species. Various species live together on earth in a harmonious proportion. This is obviously carefully regulated. One of the seemingly principal regulatory mechanisms that produces equilibrium among living organisms is brain aging. It ultimately leads to the elimination of those individuals who have already fulfilled their duty in nurturing the new generation.
Accordingly, the period from weaning until sexual maturity is reached is the most delightful phase of life, the glorious uphill journey. The individual progressively takes possession, on a mature level, of all abilities crucial for survival and maintenance of the species. It learns to avoid dangerous situations, masters the techniques to obtain its food, develops procreative powers for sexual reproduction and copulates.
This is, at the same time, the climax of developmental longevity. The fully sexually mature individual fulfills its duty. Thus, to maintain the precisely balanced out natural equilibrium among living organisms, the biologically "useless" individual has to be eliminated. According to the inborn program, the postdevelopmental stage of life (aging) begins. The essence of this stage is progressive decay of the efficiency of the catecholaminergic system during the postdevelopmental life span until at some point, in an emergency situation, the integration of the parts in a highly sophisticated entity can no longer be maintained and "natural death," signaled by the disappearance of the EEG signal, sets in.
Regarding the quality and duration of life, the most important aging process is the continuous, slow, age-related decline of the mesencephalic enhancer regulation during the postdevelopment phase of life. This can not be reversed, but its progress can be slowed by the prophylactic administration of a synthetic mesencephalic enhancer substance (for the time being with the daily administration of one milligram of deprenyl). The earlier this protective treatment starts, the better are the prospects to improve the quality of life in the latter decades, which necessarily goes together with an extension of life span.
The average life span in the most developed countries has already exceeded the eighty year level. This change has come about due to the prevention of premature deaths owing to the development of hygiene, immunology, and chemotherapy. The human technical life span (TLSh), close to one hundred twenty years, has remained, however, unchanged.
In Knoll's view, to extend the human life span beyond the TLSh needs the elaboration of an ultimate technique for the prophylactic, daily small-dose administration of a safe synthetic mesencephalic enhancer substance from sexual maturity until death. The attainable upper limit in the extension of the TLSh is obviously unpredictable at present.
Nevertheless, if brain research could, at some time in the future, achieve just a doubling of the TLSh, this will mean for humans the most significant accomplishment that science has ever achieved, since nothing can be more important for the individual than the quality and duration of his/her life.
In the developed countries the proportion of the aged is high, and the estimated number of individuals over sixty-five will increase to 1.1 billion by 2050. Accordingly, the demand on anti-aging therapy is rapidly increasing. This trend explains the already high-sounding proposals for anti-aging treatments.
Since the brain alone ensures that the mammalian organism works as a purposeful, motivated, goal-directed entity, the age-related changes in the central nervous system are of particular importance. And since the enhancer-sensitive neurons in the brain stem work as the engine of the brain, the slow, continuous, postdevelopmental functional decline of the mesencephalic enhancer regulation is of primary importance in the maintenance of the well-balanced equilibrium among living organisms, because it helps to eliminate the individuals who already fulfilled their duty in nurturing the new generation.
For the time being the prestigious task—the maintenance of the mesencephalic enhancer regulation during the postdevelopmental phase of life on the enhanced level characteristic of developmental longevity—cannot be fully accomplished. However, it is already feasible to modestly slow the age-related decay of the catecholaminergic and trace-aminergic tone in the brain via the prophylactic administration of one milligram of deprenyl daily.
The development of BPAP—a synthetic mesencephalic enhancer substance that is at least a hundred times more potent than deprenyl—is by itself a hint that our present knowledge about the mesencephalic enhancer regulation is in a very early stage. Better understanding of mesencephalic enhancer regulation promises to develop more efficient techniques in the future to slow brain aging and prolong human life beyond the TLSh. This physiologically well-founded, feasible, antiaging therapy is likely to remain a method to continuously improve the quality, and prolong the duration of human life.
Humans cannot change natural laws, but by discovering their mechanisms of action they learn to make use of this knowledge. By conquering gravitation man stepped across his naturally given limit and ultimately landed on the moon. By conquering the age-related decline of the mesencephalic enhancer regulation man might in the future step across also this naturally given limit and extend human life span beyond the TLSh.
Dr. Knoll's ambition is to develop a more efficient compound than deprenyl for slowing the age-related decay of the mesencephalic enhancer regulation, and to detect the envisioned unknown mesencephalic enhancer substances, expected to be several thousand times more active than PEA or tryptamine. Currently we are trying to clarify in more detail the pharmacological spectrum of BPAP—our newly developed, tryptamine-derived, synthetic mesencephalic enhancer substance.
DOPAMINE
The neurotransmitter dopamine is very important but is much less well known than serotonin. Remember that much of what we know about the function of the different neurotransmitters has been discovered by studying the effects of pharmaceuticals with known mechanisms of action that involve neurotransmitter levels. It’s also important to note that changes in the levels or activity of one neurotransmitter will usually affect the level and activity of other neurotransmitters. For example the chronic use of SSRI drugs which increase serotonin often show the unwanted side effects called “poop out” syndrome. This is characterized by decreased libido, motivation, creativity, drive and initiative but without depressed mood. The theory is that such changes occur because the extra serotonin blocks dopamine in other parts of the brain. Even if the SSRI is increased, these symptoms probably will not improve. The SSRI must be decreased or another agent added, or proper supplementation utilized to increase dopamine signaling in the prefrontal cortex.
As suggested above, dopamine is important for a variety of mental functions not necessarily related to anxiety or depression. Neurons which depend on dopamine for neurotransmission (dopaminergic neurons) are found in the limbic system, the mid-cortex, the nigrostriatal region, and the tuberoinfundibular bundles (related to prolactin levels). The typical antipsychotic drugs that have long been in use by psychiatrists work because they tune down the excess dopamine effects in the limbic system that produce positive psychotic symptoms (ie phenomena that should not normally occur) such as hallucinations and delusions. However, psychotic patients also suffer from thinking and motivation disturbances (the so called negative psychotic symptoms…ie things that should be present but are not) which is due to inadequate dopamine stimulation of the midcortex. Therefore by further blocking dopamine’s effect, the typical antipsychotic drugs help the “crazy” symptoms but also make the average patient more like a “zombie” who lacks drive, energy, vitality, and libido. Some of these “unwanted” effects have been specifically exploited in institutions using these drugs as “chemical restraints” in chronic mental patients, sex offenders, and the criminally insane. The other unwanted effect of these drugs is a symptom complex that looks just like Parkinson’s disease (extrapyramidal symptoms). This occurs because they artificially reduce dopamine effect in the nigrostriatal area, specifically the substantia nigra, which is the same part of the brain where natural depletion of dopamine eventually results in Parkinson’s disease. If you think of what a Parkinson’s disease patient looks like, stiff, immobile, lack of expression on the face, tremulous, slow reaction time you can see the end point of dopamine depletion.
With that lesson in pharmacology as a backdrop then, what do we need to know about dopamine? First, dopamine effect can be diminished by interference from the serotonin effects of the SSRI class of drugs. One goes up the other goes down. In human physiology there are many interrelationships and balances between chemical messengers. Using SSRI drugs or nutrients that increase serotonin may lead to depletion of dopamine with its associated symptoms. Second, the aging process takes an inevitable toll on dopaminergic neurons via oxidative stress. The most dramatic manifestation of that process is Parkinson’s disease, previously known as the “shaking palsy”. Theoretically if man lived long enough, the incidence of Parkinson’s disease would approach 100%. Dopamine content of the brain is stable until age 45, and then decreases linearly about 13% every decade. When the loss of dopamine reaches 30% Parkinsonian symptoms may begin. I feel the rate of decay in dopamine content is subject to modification by nutritional and other interventions.
Third, we should be aware of the earlier manifestations of the loss of dopaminergic neurons. Loss of drive and vitality is the clearest signal, along with poor motivation, loss of joy generally, low sex drive, diminished sexual performance and pleasure from sexual activity, and lessened intensity of orgasms are common. Another, even earlier, sign of trouble is the inability to remember one’s dreams, or a complete discontinuation of dream activity. The beta waves on a brain EEG are the ones associated with alertness and they originate in the frontal lobes of the brain from neurons that produce and depend on dopamine, which controls the electrical voltage of your brain. Overall dopamine works as a natural amphetamine that controls your energy, excitement and motivation. It is also related to blood pressure, metabolism, digestion, voluntary movement, intelligence, abstract thought, setting goals, and long-term planning.
Those individuals with a predominant dopamine nature who are balanced know what they want, are assertive, strong-willed, fast on their feet and self-confident. Dopamine personalities tend to like facts and figures are highly rational and are achievement oriented. Dopamine types gravitate toward occupations such as law, science, allopathic medicine, engineering, architecture and the military.
Producing too much dopamine can make one too intense, compulsive and driven. Overproduction of dopamine can also lead to violent behavior. Dopamine deficiencies can lead to some of the following symptoms:
Anemia
Blood sugar instability
Bone density loss
High blood pressure
Low sex drive and/or difficulty achieving orgasm
Joint pain
Thyroid disorders
Aggression (paradoxically)
Anger
Depression
Inability to handle stress
Guilt or feelings of worthlessness
Excessive sleep
Mood swings
Slow thought processing speed
Forgetfulness
Attention deficit disorder
Hyperactivity
Failure to finish tasks
Severe dopamine deficiencies are often treated with medications or hormones. Mild to moderate dopamine deficiencies can be balanced with diet, supplements and lifestyle modifications. Physical signs of dopamine deficiency will be fatigue, sleeping long hours and still not feeling rested, your mind wandering, difficulty making decisions, craving caffeine, sexual dysfunction. Unconsciously you will try to compensate by avoiding stressful situations, drinking coffee to give you energy and drinking alcohol to bring you down. It is important once you realize this to correct your underlying dopamine deficiency with proper nutrition, supplementation and lifestyle modifications.
Other strategies that the person interested in anti-aging medicine may employ include lifelong antioxidant supplementation which may slow the rapid deterioration in neuron health and dopamine levels later in life. Furthermore, each of the primary neurotransmitters has a nutrient precursor, and dopamine is derived from the amino acids phenylalanine and tyrosine. Co-factors such as folic acid, vitamin B6, iron, copper and vitamin C are important for phenylanaline to be absorbed and utilized, but phenylalanine is not a useful supplement to employ in the attempt to raise dopamine levels. There are too many other pathways whereby the body utilizes that amino acid, therefore most of it is NOT used in the production of dopamine. Instead, extra vitamin B6 (which increases tyrosine peroxidase, which increases dopamine) as a supplement as soon as loss of dream recall begins to occur makes sense. The amino acid tyrosine is a more direct precursor to dopamine, and can also be usefully prescribed in those on SSRI or antipsychotic drugs, or amino acid therapy targeting serotonin levels in order to prevent/correct dopamine depletion. Macuna pruriens is a supplement that contains a naturally occurring form of dopamine. A pharmaceutical of great interest in the battle against neuron death and dropping dopamine levels is deprenyl. This is one of the drugs which inhibits the enzyme monoamine oxidase and therefore increases dopamine effect at the neuron synaptic junctions. Apart from being one of the most indicated drugs for Parkinson’s disease (a dopamine deficiency disease), in lower doses and in the right form it is an excellent way to restore full function of dopamine dependent parts of the brain. It also prevents neuron cell death by enhancing certain antioxidant levels. This medication requires a prescription, and should be used under an anti-aging physicians guidance, but all the literature suggests that deprenyl may be a premiere preventative and treatment for age related mental, emotional, and physical decline.
Dopamine is a crucially important brain neurotransmitter. Deficiencies or imbalances can be diagnosed by clinical symptoms and urine neurotransmitter evaluation. Natural remedy and safe low dose pharmaceutical treatments are available and effective in restoring balance, reducing symptoms, slowing aging, and enhancing quality of life.
As suggested above, dopamine is important for a variety of mental functions not necessarily related to anxiety or depression. Neurons which depend on dopamine for neurotransmission (dopaminergic neurons) are found in the limbic system, the mid-cortex, the nigrostriatal region, and the tuberoinfundibular bundles (related to prolactin levels). The typical antipsychotic drugs that have long been in use by psychiatrists work because they tune down the excess dopamine effects in the limbic system that produce positive psychotic symptoms (ie phenomena that should not normally occur) such as hallucinations and delusions. However, psychotic patients also suffer from thinking and motivation disturbances (the so called negative psychotic symptoms…ie things that should be present but are not) which is due to inadequate dopamine stimulation of the midcortex. Therefore by further blocking dopamine’s effect, the typical antipsychotic drugs help the “crazy” symptoms but also make the average patient more like a “zombie” who lacks drive, energy, vitality, and libido. Some of these “unwanted” effects have been specifically exploited in institutions using these drugs as “chemical restraints” in chronic mental patients, sex offenders, and the criminally insane. The other unwanted effect of these drugs is a symptom complex that looks just like Parkinson’s disease (extrapyramidal symptoms). This occurs because they artificially reduce dopamine effect in the nigrostriatal area, specifically the substantia nigra, which is the same part of the brain where natural depletion of dopamine eventually results in Parkinson’s disease. If you think of what a Parkinson’s disease patient looks like, stiff, immobile, lack of expression on the face, tremulous, slow reaction time you can see the end point of dopamine depletion.
With that lesson in pharmacology as a backdrop then, what do we need to know about dopamine? First, dopamine effect can be diminished by interference from the serotonin effects of the SSRI class of drugs. One goes up the other goes down. In human physiology there are many interrelationships and balances between chemical messengers. Using SSRI drugs or nutrients that increase serotonin may lead to depletion of dopamine with its associated symptoms. Second, the aging process takes an inevitable toll on dopaminergic neurons via oxidative stress. The most dramatic manifestation of that process is Parkinson’s disease, previously known as the “shaking palsy”. Theoretically if man lived long enough, the incidence of Parkinson’s disease would approach 100%. Dopamine content of the brain is stable until age 45, and then decreases linearly about 13% every decade. When the loss of dopamine reaches 30% Parkinsonian symptoms may begin. I feel the rate of decay in dopamine content is subject to modification by nutritional and other interventions.
Third, we should be aware of the earlier manifestations of the loss of dopaminergic neurons. Loss of drive and vitality is the clearest signal, along with poor motivation, loss of joy generally, low sex drive, diminished sexual performance and pleasure from sexual activity, and lessened intensity of orgasms are common. Another, even earlier, sign of trouble is the inability to remember one’s dreams, or a complete discontinuation of dream activity. The beta waves on a brain EEG are the ones associated with alertness and they originate in the frontal lobes of the brain from neurons that produce and depend on dopamine, which controls the electrical voltage of your brain. Overall dopamine works as a natural amphetamine that controls your energy, excitement and motivation. It is also related to blood pressure, metabolism, digestion, voluntary movement, intelligence, abstract thought, setting goals, and long-term planning.
Those individuals with a predominant dopamine nature who are balanced know what they want, are assertive, strong-willed, fast on their feet and self-confident. Dopamine personalities tend to like facts and figures are highly rational and are achievement oriented. Dopamine types gravitate toward occupations such as law, science, allopathic medicine, engineering, architecture and the military.
Producing too much dopamine can make one too intense, compulsive and driven. Overproduction of dopamine can also lead to violent behavior. Dopamine deficiencies can lead to some of the following symptoms:
Anemia
Blood sugar instability
Bone density loss
High blood pressure
Low sex drive and/or difficulty achieving orgasm
Joint pain
Thyroid disorders
Aggression (paradoxically)
Anger
Depression
Inability to handle stress
Guilt or feelings of worthlessness
Excessive sleep
Mood swings
Slow thought processing speed
Forgetfulness
Attention deficit disorder
Hyperactivity
Failure to finish tasks
Severe dopamine deficiencies are often treated with medications or hormones. Mild to moderate dopamine deficiencies can be balanced with diet, supplements and lifestyle modifications. Physical signs of dopamine deficiency will be fatigue, sleeping long hours and still not feeling rested, your mind wandering, difficulty making decisions, craving caffeine, sexual dysfunction. Unconsciously you will try to compensate by avoiding stressful situations, drinking coffee to give you energy and drinking alcohol to bring you down. It is important once you realize this to correct your underlying dopamine deficiency with proper nutrition, supplementation and lifestyle modifications.
Other strategies that the person interested in anti-aging medicine may employ include lifelong antioxidant supplementation which may slow the rapid deterioration in neuron health and dopamine levels later in life. Furthermore, each of the primary neurotransmitters has a nutrient precursor, and dopamine is derived from the amino acids phenylalanine and tyrosine. Co-factors such as folic acid, vitamin B6, iron, copper and vitamin C are important for phenylanaline to be absorbed and utilized, but phenylalanine is not a useful supplement to employ in the attempt to raise dopamine levels. There are too many other pathways whereby the body utilizes that amino acid, therefore most of it is NOT used in the production of dopamine. Instead, extra vitamin B6 (which increases tyrosine peroxidase, which increases dopamine) as a supplement as soon as loss of dream recall begins to occur makes sense. The amino acid tyrosine is a more direct precursor to dopamine, and can also be usefully prescribed in those on SSRI or antipsychotic drugs, or amino acid therapy targeting serotonin levels in order to prevent/correct dopamine depletion. Macuna pruriens is a supplement that contains a naturally occurring form of dopamine. A pharmaceutical of great interest in the battle against neuron death and dropping dopamine levels is deprenyl. This is one of the drugs which inhibits the enzyme monoamine oxidase and therefore increases dopamine effect at the neuron synaptic junctions. Apart from being one of the most indicated drugs for Parkinson’s disease (a dopamine deficiency disease), in lower doses and in the right form it is an excellent way to restore full function of dopamine dependent parts of the brain. It also prevents neuron cell death by enhancing certain antioxidant levels. This medication requires a prescription, and should be used under an anti-aging physicians guidance, but all the literature suggests that deprenyl may be a premiere preventative and treatment for age related mental, emotional, and physical decline.
Dopamine is a crucially important brain neurotransmitter. Deficiencies or imbalances can be diagnosed by clinical symptoms and urine neurotransmitter evaluation. Natural remedy and safe low dose pharmaceutical treatments are available and effective in restoring balance, reducing symptoms, slowing aging, and enhancing quality of life.
Dopoamine - A Molecule of Motivation
...an experiment created a freakish strain of laboratory mouse that lacks all motivation to eat... is physically capable of eating, likes the taste of food in its mouth, it will chew and swallow, all the while wriggling its nose in apparent rodent satisfaction if fed. Yet left on its own, the mouse will not rouse itself ... with overwhelming apathy... Days pass, the mouse doesn’t eat, it hardly moves, and within a couple of weeks, it has starved itself to death.
Behind the rodent’s fatal case of ennui is a severe deficit of dopamine, one of the essential signaling molecules in the brain. Dopamine has lately become quite fashionable, today’s “it” neurotransmitter, just as serotonin was “it” in the Prozac-laced ’90s.
“dopamine rush” — anything that imparts a small, pleasurable thrill. Familiar agents of vice like cocaine, methamphetamine, alcohol and nicotine are known to stimulate the brain’s dopamine circuits, as do increasingly popular stimulants like Adderall and Ritalin.
In the communal imagination, dopamine is about rewards, and feeling good, and wanting to feel good again, and if you don’t watch out, you’ll be hooked, a slave to the pleasure coursing through your brain.
Yet as new research on dopamine-deficient mice and other studies reveal, the image of dopamine as about pleasure transmission in the brain is misleading.
In the emerging view, dopamine is less about pleasure and reward than about drive and motivation, about figuring out what you have to do to survive and then doing it... the gasping for oxygen and the wolfing down of food when starved, shows the dopamine pathways of the brain are at full throttle. The whole brain is of one mindset the intense drive to get you out of a state of deprivation and keep you alive.
Dopamine is also part of the brain’s salience filter, its get-a-load-of-this device. “You can’t pay attention to everything, but you want to be adept as an organism at recognizing things that are novel,” Dr. Volkow said. “You might not notice a fly in the room, but if that fly was fluorescent, your dopamine cells would fire.”
In addition, our dopamine-driven salience detector will focus on familiar objects that we have imbued with high value, both positive and negative: objects we want and objects we fear. Dopamine makes a relevant object almost impossible to ignore.
There is also dopamine activity in the prefrontal cortex, the great executive brain. An impoverishment of prefrontal dopamine is thought to contribute to schizophrenia.
Scientists say that ADHD may be the result of reduced dopamine levels in the brain. Dopamine does many things in the brain, and plays important roles in behavior and thinking, attention, learning, motor activity, regulation of milk production, motivation and reward, sleep, and mood. This brain chemical is very important in the ADHD symptoms of hyperactivity, attention, motor activity, and the tendency to substance abuse.
What has been found is that the ADHD subjects have much lower levels of dopamine than their healthy counterparts. This was also true in parts of the limbic system, which controls emotional responses and memory.
People differ from one another at every juncture of the dopamine matrix, in the tonal background pace at which their dopamine neurons rhythmically fire, the avidity with which the cells spike in response to need or news, and the ease with which hyperstimulated cells revert to baseline.
Some researchers have looked at genetic variations in receptor types for clues to personality differences. According to Dan T. A. Eisenberg of Northwestern University, scientists have detected a modest connection between a relatively elongated version of dopamine receptor No. 4 and a tendency toward impulsivity and risk-taking behavior, particularly financial risk-taking... preliminary correlations in behavioral genetics ...
Source: NYT online
By NATALIE ANGIER
Behind the rodent’s fatal case of ennui is a severe deficit of dopamine, one of the essential signaling molecules in the brain. Dopamine has lately become quite fashionable, today’s “it” neurotransmitter, just as serotonin was “it” in the Prozac-laced ’90s.
“dopamine rush” — anything that imparts a small, pleasurable thrill. Familiar agents of vice like cocaine, methamphetamine, alcohol and nicotine are known to stimulate the brain’s dopamine circuits, as do increasingly popular stimulants like Adderall and Ritalin.
In the communal imagination, dopamine is about rewards, and feeling good, and wanting to feel good again, and if you don’t watch out, you’ll be hooked, a slave to the pleasure coursing through your brain.
Yet as new research on dopamine-deficient mice and other studies reveal, the image of dopamine as about pleasure transmission in the brain is misleading.
In the emerging view, dopamine is less about pleasure and reward than about drive and motivation, about figuring out what you have to do to survive and then doing it... the gasping for oxygen and the wolfing down of food when starved, shows the dopamine pathways of the brain are at full throttle. The whole brain is of one mindset the intense drive to get you out of a state of deprivation and keep you alive.
Dopamine is also part of the brain’s salience filter, its get-a-load-of-this device. “You can’t pay attention to everything, but you want to be adept as an organism at recognizing things that are novel,” Dr. Volkow said. “You might not notice a fly in the room, but if that fly was fluorescent, your dopamine cells would fire.”
In addition, our dopamine-driven salience detector will focus on familiar objects that we have imbued with high value, both positive and negative: objects we want and objects we fear. Dopamine makes a relevant object almost impossible to ignore.
There is also dopamine activity in the prefrontal cortex, the great executive brain. An impoverishment of prefrontal dopamine is thought to contribute to schizophrenia.
Scientists say that ADHD may be the result of reduced dopamine levels in the brain. Dopamine does many things in the brain, and plays important roles in behavior and thinking, attention, learning, motor activity, regulation of milk production, motivation and reward, sleep, and mood. This brain chemical is very important in the ADHD symptoms of hyperactivity, attention, motor activity, and the tendency to substance abuse.
What has been found is that the ADHD subjects have much lower levels of dopamine than their healthy counterparts. This was also true in parts of the limbic system, which controls emotional responses and memory.
People differ from one another at every juncture of the dopamine matrix, in the tonal background pace at which their dopamine neurons rhythmically fire, the avidity with which the cells spike in response to need or news, and the ease with which hyperstimulated cells revert to baseline.
Some researchers have looked at genetic variations in receptor types for clues to personality differences. According to Dan T. A. Eisenberg of Northwestern University, scientists have detected a modest connection between a relatively elongated version of dopamine receptor No. 4 and a tendency toward impulsivity and risk-taking behavior, particularly financial risk-taking... preliminary correlations in behavioral genetics ...
Source: NYT online
By NATALIE ANGIER
Friday, August 21, 2009
Bohm talks to Krishnamurti
THE FUTURE OF HUMANITY is a dialogue between J. Krishnamurti and David Bohm which took place in Brockwood Park, England in 1983. Starting with the questions - Are psychologists really concerned with the future of man? Are they concerned with the human being conforming to the present society, or going beyond that? - the conversation embarks on the incredible journey of the unconditioned mind and asks if the consciousness of mankind can be changed through time.
Defeat your noise machine
Tolle calls your mind a noise machine. He stepped outside his noise machine and ended his debilitating depression by changing the story he told himself was his life.
I like that idea and I think further that if we can separate our conciousnees and call the noise machine our working mind and use it to navigate the world while holding onto a higher conciousness that exists without the me conciousness that drives the noise machine we will be a better integrated being.
I like that idea and I think further that if we can separate our conciousnees and call the noise machine our working mind and use it to navigate the world while holding onto a higher conciousness that exists without the me conciousness that drives the noise machine we will be a better integrated being.
Subscribe to:
Posts (Atom)