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Discovery of post-stimulus activated release implies new mechanisms for dopamine release
October 16, 2006The neurotransmitter dopamine continues to be released for nearly an hour after neurons are stimulated, suggesting the existence of secondary mechanisms that allow for sustained availability of dopamine in different regions of the brain including areas critical for memory consolidation, drug induced plasticity and maintaining active networks during working memory, according to a University of Pittsburgh study being presented today at the 36th Annual Meeting of the Society for Neuroscience, held at the Georgia World Congress Center in Atlanta.
Determining the mechanisms that cause what is being called "post-stimulus activated release" and how they maintain dopamine levels could have important implications for understanding and treating neurological and psychiatric disorders caused by an imbalance of dopamine function including schizophrenia, attention deficit hyperactivity disorder, Tourette's syndrome, Parkinson's disease and addiction.
According to Bita Moghaddam, Ph.D., professor of neuroscience and psychiatry, who led the study, in addition to its clinical benefits, post-stimulus activated release can be used to explain how brief events that activate neurons for short periods of time can influence brain function long after the events. For example, it can be used to explain how smelling freshly baked cookies could evoke childhood memories of spending time with a beloved grandparent, leading a person to reminisce long after the smell is gone and take the unplanned or impulsive action of baking or buying cookies.
Dopamine is a neurotransmitter associated with learning and memory, motor control, reward perception and executive functions such as working memory, behavioral flexibility and decision making. When a novel or salient stimulus occurs, the dopamine neurons in the brain increase their firing rate, boosting the release of dopamine. The dopamine is diffused into the extracellular space of the brain until it can be transported or metabolized.
In a rat model, the researchers have been attempting to understand increases in extracellular levels of dopamine during behaviorally active states, such as completing a cognitive task or experiencing stressful situations and in response to the electrical stimulation of neurons. In their studies, they have observed that dopamine levels remain above the baseline long after neurons had been stimulated - from five to 20 minutes in the ventral tegmental area (VTA) and 40 to 100 minutes in the nucleus accumbens and prefrontal cortex.
Attempting to discern the cause of the elevated levels, researchers stimulated the VTA of the brain of a rat model by using an electrode. The VTA is a nucleus in the midbrain where dopamine neurons are located. After stimulating the neurons, the researchers measured the amount of dopamine in the extracellular fluid of the nucleus accumbens and prefrontal cortex - two areas where the VTA is known to send signals. They found that dopamine levels increased during stimulation, and remained elevated for an hour after stimulation.
Dopamine levels wane as dopamine is taken back into cells by an active transport system. Yet this active transport system is not abundant in the ventral striatum and prefrontal cortex areas, leading researchers to think that perhaps the dopamine levels remained elevated due to an excess that had yet to be absorbed. To test this hypothesis, they applied tetrodotoxin (TTX), a neurotoxin that blocks the active release of dopamine, to the nucleus accumbens and prefrontal cortex. TTX caused dopamine levels to drop, indicating that the dopamine levels remained elevated because dopamine was being actively released after the neurons fired and not because there was residual dopamine in the brain.
Dr. Moghaddam and colleagues are currently conducting experiments in efforts to identify the exact mechanism causing post-stimulus activated release.
University of Pittsburgh Medical Center
Dopamine is a neurotransmitter associated with learning and memory, motor control, reward perception and executive functions such as working memory, behavioral flexibility and decision making. When a novel or salient stimulus occurs, the dopamine neurons in the brain increase their firing rate, boosting the release of dopamine. The dopamine is diffused into the extracellular space of the brain until it can be transported or metabolized.
In a rat model, the researchers have been attempting to understand increases in extracellular levels of dopamine during behaviorally active states, such as completing a cognitive task or experiencing stressful situations and in response to the electrical stimulation of neurons. In their studies, they have observed that dopamine levels remain above the baseline long after neurons had been stimulated - from five to 20 minutes in the ventral tegmental area (VTA) and 40 to 100 minutes in the nucleus accumbens and prefrontal cortex.
Attempting to discern the cause of the elevated levels, researchers stimulated the VTA of the brain of a rat model by using an electrode. The VTA is a nucleus in the midbrain where dopamine neurons are located. After stimulating the neurons, the researchers measured the amount of dopamine in the extracellular fluid of the nucleus accumbens and prefrontal cortex - two areas where the VTA is known to send signals. They found that dopamine levels increased during stimulation, and remained elevated for an hour after stimulation.
Dopamine levels wane as dopamine is taken back into cells by an active transport system. Yet this active transport system is not abundant in the ventral striatum and prefrontal cortex areas, leading researchers to think that perhaps the dopamine levels remained elevated due to an excess that had yet to be absorbed. To test this hypothesis, they applied tetrodotoxin (TTX), a neurotoxin that blocks the active release of dopamine, to the nucleus accumbens and prefrontal cortex. TTX caused dopamine levels to drop, indicating that the dopamine levels remained elevated because dopamine was being actively released after the neurons fired and not because there was residual dopamine in the brain.
Dr. Moghaddam and colleagues are currently conducting experiments in efforts to identify the exact mechanism causing post-stimulus activated release.
University of Pittsburgh Medical Center
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ISU researchers' findings bring hope for possible Parkinson's disease cure
Researchers at Iowa State University have found an essential key to possibly cure Parkinson's disease and are looking for others.
Widely used cholesterol-lowering drug may prevent progression
Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.
Stress-induced changes in brain circuitry linked to cocaine relapse
Stress-evoked changes in circuits that regulate serotonin in certain parts of the brain can precipitate a low mood and a relapse in cocaine-seeking, based on mouse studies published online this week in the Proceedings of the National Academy of Sciences.
Researchers find brain cell transplants help repair neural damage
A Swiss research team has found that using an animal's own brain cells (autologous transplant) to replace degenerated neurons in select brain areas of donor primates with simulated but asymptomatic Parkinson's disease and previously in a motor cortex lesion model, provides a degree of brain protection and may be useful in repairing brain lesions and restoring function.
Changes in brain chemicals mark shifts in infant learning
When do you first leave the nest? Early in development infants of many species experience important transitions-such as learning when to leave the protective presence of their mother to start exploring the wider world.
Why antidepressants don't work for so many
More than half the people who take antidepressants for depression never get relief.
Cocaine exposure during pregnancy leads to impulsivity in male, not female, monkeys
Adult male monkeys exposed to cocaine while in the womb have poor impulse control and may be more vulnerable to drug abuse than female monkeys, even a decade or more after the exposure, according to a new study by researchers at Wake Forest University School of Medicine. The findings could lead to a better understanding of human drug abuse.
Scientists demonstrate link between genetic defect and brain changes in schizophrenia
Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.
Fine-tuning treatments for depression
New research clarifies how neurotransmitters like norepinephrine, serotonin, and dopamine, are regulated - a finding that may help fine-tune therapies for depression.
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Dopamine Handbook by Leslie Iversen (Author), Susan Iversen (Author), Stephen Dunnett (Author), Anders Bjorklund (Author) The discovery of dopamine in 1957-1958 was one of the seminal events in the development of modern neuroscience, and has been extremely important for the development of modern therapies of neurological and psychiatric disorders. Dopamine has a fundamental role in almost all aspects of behavior: from motor control to mood regulation, cognition and addiction and reward, and dopamine research has been unique within the neurosciences in the way it has bridged basic science and clinical practice. Over the decades research into the role of dopamine in health and disease has been in the forefront of modern neuroscience. The Dopamine Handbook is the first single-volume publication to capture current progress and excitement in this dynamic research field. |
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Imaging Dopamine by Paul Cumming (Author) Since its discovery 50 years ago, brain dopamine has been implicated in the control of movement and cognition, and is concerned with diverse brain diseases such as Parkinson's disease, schizophrenia and drug addiction. This book is an illustrated biography of the dopamine molecule, from its synthesis in the brain to its signalling mechanisms and ultimately to its metabolic breakdown. Using colour illustrations of positron emission tomography (PET) scans, each chapter presents a specific stage in the biochemical pathway for dopamine. Writing for researchers and graduate students, Paul Cumming presents a compilation of all that has been learned about dopamine through molecular imaging, a technology which allows the measurement of formerly invisible processes in the living brain. He reviews... |
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Dopamine Starring: John Livingston, Sabrina Lloyd, Bruno Campos, Rueben Grundy, Kathleen Antonia Directed By: Mark Decena Also With: Timothy Breitbach (Writer), Mark Decena (Writer), Andrew Jon Thomson (Producer), Brian Benson (Producer), Chris Miller (Producer), Christopher James Hall (Producer), Debbie Brubaker (Producer) A romantic drama for the modern age, Dopamine looks at the complexities of pursuing love when contemporary life and personal demons form mighty obstacles. Named after the natural chemical that our bodies produce when we fall in love, Dopamine follows the courtship between a computer animator and a kindergarten teacher and creates a soulful portrait of two people facing up to the risks and rewards of falling in love. |
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