1. Scientific discovery may change treatment of Parkinson’s

    April 3, 2017 by Ashley

    From the University of Turku press release:

    When monitoring Parkinson’s disease, SPECT imaging of the brain is used for acquiring information on the dopamine activity. A new study conducted in Turku, Finland, shows that the dopamine activity observed in SPECT imaging does not reflect the number of dopamine neurons in the substantia nigra, as previously assumed.

    One of the most significant changes in the central nervous system in Parkinson’s disease is the loss of dopamine-producing neurons in the substantia nigra, causing a drop in dopamine levels in the brain.

    “Low dopamine level in the brain is linked with the central motor symptoms of Parkinson’s disease, i.e. tremor or shaking, muscle stiffness and slowness of movements,” says Docent of Neurology Valtteri Kaasinen from the University of Turku.

    Decreased dopamine activity can be detected with a single-photon emission computed tomography (SPECT) imaging of the brain. This method is widely used in the diagnostics of Parkinson’s disease in Europe and the United States.

    The study conducted at the University of Turku and Turku University Hospital shows that the dopamine activity observed in SPECT imaging does not reflect the number of dopamine neurons in the substantia nigra, contrary to what has been thought. According to Kaasinen, this is an important result as it proves that the correlation between the number of neurons and dopamine activity is not straightforward.

    “This must be considered in the future when developing treatments that affect the number of neurons in the substantia nigra. It also seems that SPECT imaging is not a suitable method for monitoring treatment research results in advanced Parkinson’s disease when studying treatments that affect the number of neurons in the substantia nigra,” says Kaasinen.

    In the study, post-mortem neuron numbers in the substantia nigra were calculated for patients with Parkinson’s disease who had been examined with dopamine transporter SPECT before death. The number of neurons cannot be calculated during a patient’s lifetime since the substantia nigra is located deep within the midbrain where biopsy is impossible in vivo.


  2. Spiritual retreats change feel-good chemical systems in the brain

    March 28, 2017 by Ashley

    From the Thomas Jefferson University press release:

    More Americans than ever are turning to spiritual, meditative and religious retreats as a way to reset their daily life and enhance wellbeing. Now, researchers at The Marcus Institute of Integrative Health at Thomas Jefferson University show there are changes in the dopamine and serotonin systems in the brains of retreat participants. The team published their results in Religion, Brain & Behavior.

    “Since serotonin and dopamine are part of the reward and emotional systems of the brain, it helps us understand why these practices result in powerful, positive emotional experiences,” said Andrew Newberg, M.D., Director of Research in the Marcus Institute of Integrative Health. “Our study showed significant changes in dopamine and serotonin transporters after the seven-day retreat, which could help prime participants for the spiritual experiences that they reported.”

    The post-retreat scans revealed decreases in dopamine transporter (5-8 percent) and serotonin transporter (6.5 percent) binding, which could make more of the neurotransmitters available to the brain. This is associated with positive emotions and spiritual feelings. In particular, dopamine is responsible for mediating cognition, emotion and movement, while serotonin is involved in emotional regulation and mood.

    The study, funded by the Fetzer Institute, included 14 Christian participants ranging in age from 24 to 76. They attended an Ignatian retreat based on the spiritual exercises developed by St. Ignatius Loyola who founded the Jesuits. Following a morning mass, participants spent most of the day in silent contemplation, prayer and reflection and attended a daily meeting with a spiritual director for guidance and insights. After returning, study subjects also completed a number of surveys which showed marked improvements in their perceived physical health, tension and fatigue. They also reported increased feelings of self-transcendence which correlated to the change in dopamine binding.

    “In some ways, our study raises more questions than it answers,” said Dr. Newberg. “Our team is curious about which aspects of the retreat caused the changes in the neurotransmitter systems and if different retreats would produce different results. Hopefully, future studies can answer these questions.”


  3. Even after treatment, brains of anorexia nervosa patients not fully recovered

    March 19, 2017 by Ashley

    From the University of Colorado Anschutz Medical Campus press release:

    Even after weeks of treatment and considerable weight gain, the brains of adolescent patients with anorexia nervosa remain altered, putting them at risk for possible relapse, according to researchers at the University of Colorado Anschutz Medical Campus.

    The study, published last week in the American Journal of Psychiatry, examined 21 female adolescents before and after treatment for anorexia and found that their brains still had an elevated reward system compared to 21 participants without the eating disorder.

    “That means they are not cured,” said Guido Frank, MD, senior author of the study and associate professor of psychiatry and neuroscience at the University of Colorado School of Medicine. “This disease fundamentally changes the brain response to stimuli in our environment. The brain has to normalize and that takes time.”

    Brain scans of anorexia nervosa patients have implicated central reward circuits that govern appetite and food intake in the disease. This study showed that the reward system was elevated when the patients were underweight and remained so once weight was restored.

    The neurotransmitter dopamine might be the key, researchers said.

    Dopamine mediates reward learning and is suspected of playing a major role in the pathology of anorexia nervosa. Animal studies have shown that food restriction or weight loss enhances dopamine response to rewards.

    With that in mind, Frank, an expert in eating disorders, and his colleagues wanted to see if this heightened brain activity would normalize once the patient regained weight. Study participants, adolescent girls who were between 15 and 16 years old, underwent a series of reward-learning taste tests while their brains were being scanned.

    The results showed that reward responses were higher in adolescents with anorexia nervosa than in those without it. This normalized somewhat after weight gain but still remained elevated.

    At the same time, the study showed that those with anorexia had widespread changes to parts of the brain like the insula, which processes taste along with a number of other functions including body self-awareness.

    The more severely altered the brain, the harder it was to treat the illness, or in other words, the more severely altered the brain, the more difficult it was for the patients to gain weight in treatment.

    Generalized sensitization of brain reward responsiveness may last long into recovery,” the study said. “Whether individuals with anorexia nervosa have a genetic predisposition for such sensitization requires further study.”

    Frank said more studies are also needed to determine if the continued elevated brain response is due to a heightened dopamine reaction to starvation and whether it signals a severe form of anorexia among adolescents that is more resistant to treatment.

    In either case, Frank said the biological markers discovered here could be used to help determine the likelihood of treatment success. They could also point the way toward using drugs that target the dopamine reward system.

    “Anorexia nervosa is hard to treat. It is the third most common chronic illness among teenage girls with a mortality rate 12 times higher than the death rate for all causes of death for females 15-24 years old,” Frank said. “But with studies like this we are learning more and more about what is actually happening in the brain. And if we understand the system, we can develop better strategies to treat the disease.”


  4. Precise technique tracks dopamine in the brain

    March 17, 2017 by Ashley

    From the MIT press release:

    brain scansMIT researchers have devised a way to measure dopamine in the brain much more precisely than previously possible, which should allow scientists to gain insight into dopamine’s roles in learning, memory, and emotion.

    Dopamine is one of the many neurotransmitters that neurons in the brain use to communicate with each other. Previous systems for measuring these neurotransmitters have been limited in how long they provide accurate readings and how much of the brain they can cover. The new MIT device, an array of tiny carbon electrodes, overcomes both of those obstacles.

    “Nobody has really measured neurotransmitter behavior at this spatial scale and timescale. Having a tool like this will allow us to explore potentially any neurotransmitter-related disease,” says Michael Cima, the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the study.

    Furthermore, because the array is so tiny, it has the potential to eventually be adapted for use in humans, to monitor whether therapies aimed at boosting dopamine levels are succeeding. Many human brain disorders, most notably Parkinson’s disease, are linked to dysregulation of dopamine.

    “Right now deep brain stimulation is being used to treat Parkinson’s disease, and we assume that that stimulation is somehow resupplying the brain with dopamine, but no one’s really measured that,” says Helen Schwerdt, a Koch Institute postdoc and the lead author of the paper, which appears in the journal Lab on a Chip.

    Studying the striatum

    For this project, Cima’s lab teamed up with David H. Koch Institute Professor Robert Langer, who has a long history of drug delivery research, and Institute Professor Ann Graybiel, who has been studying dopamine’s role in the brain for decades with a particular focus on a brain region called the striatum. Dopamine-producing cells within the striatum are critical for habit formation and reward-reinforced learning.

    Until now, neuroscientists have used carbon electrodes with a shaft diameter of about 100 microns to measure dopamine in the brain. However, these can only be used reliably for about a day because they produce scar tissue that interferes with the electrodes’ ability to interact with dopamine, and other types of interfering films can also form on the electrode surface over time. Furthermore, there is only about a 50 percent chance that a single electrode will end up in a spot where there is any measurable dopamine, Schwerdt says.

    The MIT team designed electrodes that are only 10 microns in diameter and combined them into arrays of eight electrodes. These delicate electrodes are then wrapped in a rigid polymer called PEG, which protects them and keeps them from deflecting as they enter the brain tissue. However, the PEG is dissolved during the insertion so it does not enter the brain.

    These tiny electrodes measure dopamine in the same way that the larger versions do. The researchers apply an oscillating voltage through the electrodes, and when the voltage is at a certain point, any dopamine in the vicinity undergoes an electrochemical reaction that produces a measurable electric current. Using this technique, dopamine’s presence can be monitored at millisecond timescales.

    Using these arrays, the researchers demonstrated that they could monitor dopamine levels in many parts of the striatum at once.

    “What motivated us to pursue this high-density array was the fact that now we have a better chance to measure dopamine in the striatum, because now we have eight or 16 probes in the striatum, rather than just one,” Schwerdt says.

    The researchers found that dopamine levels vary greatly across the striatum. This was not surprising, because they did not expect the entire region to be continuously bathed in dopamine, but this variation has been difficult to demonstrate because previous methods measured only one area at a time.

    How learning happens

    The researchers are now conducting tests to see how long these electrodes can continue giving a measurable signal, and so far the device has kept working for up to two months. With this kind of long-term sensing, scientists should be able to track dopamine changes over long periods of time, as habits are formed or new skills are learned.

    “We and other people have struggled with getting good long-term readings,” says Graybiel, who is a member of MIT’s McGovern Institute for Brain Research. “We need to be able to find out what happens to dopamine in mouse models of brain disorders, for example, or what happens to dopamine when animals learn something.”

    She also hopes to learn more about the roles of structures in the striatum known as striosomes. These clusters of cells, discovered by Graybiel many years ago, are distributed throughout the striatum. Recent work from her lab suggests that striosomes are involved in making decisions that induce anxiety.

    This study is part of a larger collaboration between Cima’s and Graybiel’s labs that also includes efforts to develop injectable drug-delivery devices to treat brain disorders.

    “What links all these studies together is we’re trying to find a way to chemically interface with the brain,” Schwerdt says. “If we can communicate chemically with the brain, it makes our treatment or our measurement a lot more focused and selective, and we can better understand what’s going on.”


  5. Alcoholism may be caused by dynamical dopamine imbalance

    March 15, 2017 by Ashley

    From the National Research University Higher School of Economics press release:

    Researchers from the Higher School of Economics, Ecole Normale Supérieure, Paris, Indiana University and the Russian Academy of Sciences Nizhny Novgorod Institute of Applied Physics have identified potential alcoholism mechanisms, associated with altered dopaminergic neuron response to complex dynamics of prefrontal cortex neurons affecting dopamine release.

    Interacting neuronal populations in the cerebral cortex generate electrical impulses (called action potentials), that are characterized by specific spatial and temporal patterns of neural firing (or complex neural dynamics). These firing patterns depend on the intrinsic properties of individual neurons, on the neural network connectivity and the inputs to these circuits. Taken as a basis for this computational study is the experimental evidence for a specific population of prefrontal cortex neurons that connects via excitatory synapses to dopaminergic and inhibitory ventral tegmental area (VTA) neurons. Thus, the structure of neural firing in the prefrontal cortex can directly affect dopamine cell response and dopamine release.

    Boris Gutkin leads the Theoretical Neuroscience Group at the HSE Centre for Cognition and Decision Making. One of the group’s research areas focuses on neurobiological processes leading to substance abuse and addiction — specifically, on detecting links between the neurobiological mechanisms of a drug’s action and observable behavioural reactions. In particular, the researchers use mathematical modelling to examine specific characteristics of dopaminergic neuron firing patterns and dynamics which can lead to addiction.

    Dopamine, a neurotransmitter released by dopaminergic neurons in the brain, is a chemical which plays a key role in the internal brain reward system that drives learning of motivated behavior. By acting within the reward systems in the brain (e.g. the ventral tegmental area found deep in the mid-brain; the striatum, responsible for selecting correct actions and the prefrontal cortex that controls voluntary goals and behaviors), it signals either unexpected reward or anticipation of reward resulting from a particular action or event. Thus, dopamine provides positive reinforcement of behaviours that lead to these rewards, causing them to be repeated. Conversely, where a particular action fails to produce the expected positive effect or is followed by an unpleasant event, dopamine release decreases sharply, leading to frustration and an unwillingness to repeat the behaviour in question.

    Many dopamine neurons produce these learning signals by emitting rapid bursts of spikes when the animal receives more reward than expected or pausing when there is less than expected. In order to govern the learning correctly, the number of bursts (and the dopamine released) must be proportional to the discrepancy between the received and the expected reward (for example if one expects to get 50 euros for his work, but gets 100; the dopamine activity should be proportional to 50; when one expects 50 but gets 500; the activity should signal a number proportional to 450). Hence the bigger the mismatch — the stronger the response. Yet another subgroup of dopamine neurons simply signals when stimuli are important for behaviour or not giving binary all or none responses. These binary signals then drive orienting or approach to the important behaviors. So the two dopamine cell populations have different response modes: analogue learning signal or all-or-none important alert.

    Two Modes of neuron Activity

    Recent research by Gutkin’s group conducted jointly with scientists from Indiana University (Alexey Kuznetsov, Mathematics and Christopher Lapish, Neuroscience) and the RAN Institute of Applied Physics (Denis Zakharov) suggests potential mechanisms of alcohol’s effect on dopaminergic neuronal activity. Their paper ‘Dopamine Neurons Change the Type of Excitability in Response to Stimuli’ published in PLOS features a computational model of dopamine (DA) neuron activity, describing its key properties and demonstrating that the DA neuron’s response mode can vary depending on the pattern of the synaptic input (including that from the prefrontal cortex).

    When in the first mode, the amount of dopamine released by the DA neurons reflects the learning signal propotional to the difference between what an animal or human expects and what they actually receive as a result of a certain action. When in the second DA neuron mode, dopamine release serves as a reference binary signal indicating whether or not a certain event is important. Hence the results of the computational study imply that dopamine neurons may not be two distinct populations, but are capable to move flexibly from one response mode to another depending on the nature of the signals they receive.

    In a related study, ‘Contribution of synchronized GABAergic neurons to dopaminergic neuron firing and bursting’, published in the Journal of Neurophysiology the same group suggests that in addition to direct links between DA and prefrontal cortex neurons, indirect neural inputs from the prefrontal cortex via inhibitory (GABAergic) VTA neurons should be considered. In particular, the researchers found that signals from the prefrontal cortex can cause GABAergic neurons to synchronise, producing a strong inhibitory effect on DA neurons. The study found that in some cases, such inhibitory effects can lead to paradoxical results: instead of suppressing DA neuron firing and thus decreasing dopamine release, they can multiply DA firing frequency leading to higher dopamine release and positive reinforcement.

    What It Means for Our Understanding of Alcoholism

    Experimental evidence suggests that alcohol is capable of modifying DA neuron firing patterns, both indirectly via prefrontal cortex and inhibitory VTA neurons, and directly by acting on DA neurons per se. Based on Gutkin and his collaborators findings, one can hypothesise what mechanisms may be involved.

    The VTA has about 20,000 DA neurons, in someone who is not alcoholic, some of these serve to signal that a certain stimulus has importance, while the rest transmit the error signal. A certain balance between the two types of signals is essential for good judgment and proper behaviour. Alcohol disrupts the balance by changing both the pattern of neural activity in the prefrontal cortex and DA neuron properties. This change may bias more neurons to signal importance as opposed to the error. So, under alcohol influence, any stimulus associated with alcohol is treated by DA neurons as having behavioural and motivational importance, regardless of whether or not it matches the anticipated outcome, while in the absence of alcohol, neural firing would normally be consistent with the expected and received reinforcements.

    This effect may be the reason why alcoholics may eventually develop a narrower than normal range of behavioural responses, dooming them to seek to use alcohol. In doing so, they are either unaware of potential consequences of their actions or, even if they can anticipate such consequences, this awareness has little or no effect on their behaviour. According to surveys, most alcoholics understand that they may lose their home and family and even die from binge drinking, but this rarely stops them. To properly assess the consequences of drinking, their prefrontal cortex needs to integrate and learn to properly represent the negative expectations from this behaviour, supported by reinforcement learning signals from DA neurons. This may not happen, however, because alcohol (like other mood-altering substances) can affect both the neural activity in the addict’s prefrontal cortex and their DA neurons directly, blocking the learning.

    Finding a way to balance out the dopamine function in the addicted brain and to elicit adequate neural responses to environmental stimuli even under the influence could offer hope to people with substance abuse problems.


  6. Dopamine neurons factor ambiguity into predictions enabling us to ‘win big and win often’

    by Ashley

    From the Cold Spring Harbor Laboratory press release:

    In the struggle of life, evolution rewards animals that master their circumstances, especially when the environment changes fast. If there is a recipe for success, it is not: savor your victories when you are fortunate to have them. Rather it is: win big, and win often.

    To make winning decisions, animals cannot consult a hard-wired playbook or receive helpful advice. Instead, success depends on their ability to learn, from triumphs and from mistakes.

    Today in the journal Current Biology, a team led by Professor Adam Kepecs of Cold Spring Harbor Laboratory (CSHL) adds an important new dimension to our understanding of how the brain learns, focusing specifically on situations in which perceptually ambiguous information is used to make predictions.

    What if it’s gotten foggy and we can barely see the sign up ahead, or the announcement over the loudspeaker is garbled? In circumstances like these, how does the brain adjust the predictions that inform decisions?

    Kepecs and colleagues describe how dopamine-releasing neurons, which are understood to produce critical teaching signals for the brain, weigh the ambiguity of sensory information when they assess how successfully past experiences have guided a new decision. Their findings indicate that these neurons are even more sophisticated than previously thought.

    “Dopamine neurons are not just any neurons in the brain,” Kepecs says. “They are neurons that sit in the midbrain and send connections to large swaths of the brain. Dopamine neurons compare the predicted outcomes to actual outcomes, and send the discrepancy between these as an error feedback to other parts of the brain. This is exactly what you would want learning signals to do. And we’ve found that what dopamine neurons do is in perfect agreement with what is theoretically required for a powerful learning algorithm.”

    This is such an effective way of learning that the same strategy, called reinforcement learning, has been incorporated into many types of artificial intelligence, allowing computers to figure out how to do things without instructions from a programmer.

    Kepecs and his team added what computer scientists call a belief state (a probability distribution variable) to a mathematical model of reinforcement learning. The previously used model is good at explaining how an animal learns from experience — but only when the sensory stimuli available to the animal are straightforward, easy to interpret. “It’s been unclear whether or how dopamine neurons factor perceptual ambiguity into their teaching signal,” Kepecs says. “Our revised model generates an estimate of the probability that a given choice is correct — this is the degree of confidence about the decision.”

    “If you can evaluate your decision process — the noise and everything else that’s contributed to it — and in addition to making a binary choice assign a graded level of confidence to the decision, it’s essentially a prediction about your accuracy,” he says. “It’s a completely different computation than just using the cues to recall past experiences to make predictions.”

    Armin Lak, a British Iranian postdoctoral researcher working with Kepecs, developed a computer model that predicted how neurons would behave if they were performing this calculation. Then they compared those predictions to the activity of dopamine neurons in the brains of monkeys while they performed a task in which they made a decision informed by visual cues that were sometimes clear, and sometimes not.

    The activity of the neurons was recorded by Kepecs’ collaborators Kensaku Nomoto and Masamichi Sakagami, neuroscientists at Tamagawa University in Tokyo, who were studying how the brain uses sensory information to make decisions. In the task, monkeys watched a screen filled with moving dots, and had to decide whether more dots were moving to the left or to the right, receiving a juice reward when they got the answer right.

    When Kepecs and Lak analyzed the data, they found that the activity of the dopamine neurons closely fit the predictions of their new model — indicating that these neurons were likely evaluating the reliability of the information used during each decision. Applying the computational model was like looking at the data through a new microscope, Kepecs says. “By looking at it this way, you can see things that you couldn’t see before in the data. Suddenly it just made sense. This system is much smarter than we thought before.”

    Surprisingly, Kepecs says, the confidence-signaling neurons became active a fraction of a second before the monkeys’ made a decision. This early activity suggests the neurons may influence the immediate decision making process — a role that the team will explore in future research.


  7. How dopamine governs ongoing decisions

    March 13, 2017 by Ashley

    From the Salk Institute media release:

    Say you’re reaching for the fruit cup at a buffet, but at the last second you switch gears and grab a cupcake instead. Emotionally, your decision is a complex stew of guilt and mouth-watering anticipation. But physically it’s a simple shift: instead of moving left, your hand went right. Such split-second changes interest neuroscientists because they play a major role in diseases that involve problems with selecting an action, like Parkinson’s and drug addiction.

    In the March 9, 2017 online publication of the journal Neuron, scientists at the Salk Institute report that the concentration of a brain chemical called dopamine governs decisions about actions so precisely that measuring the level right before a decision allows researchers to accurately predict the outcome. Additionally, the scientists found that changing the dopamine level is sufficient to alter upcoming choice. The work may open new avenues for treating disorders both in cases where a person cannot select a movement to initiate, like Parkinson’s disease, as well as those in which someone cannot stop repetitive actions, such as obsessive-compulsive disorder (OCD) or drug addiction.

    “Because we cannot do more than one thing at a time, the brain is constantly making decisions about what to do next,” says Xin Jin, an assistant professor in Salk’s Molecular Neurobiology Laboratory and the paper’s senior author. “In most cases our brain controls these decisions at a higher level than talking directly to particular muscles, and that is what my lab mostly wants to understand better.”

    When we decide to perform a voluntary action, like tying our shoelaces, the outer part of our brain (the cortex) sends a signal to a deeper structure called the striatum, which receives dopamine to orchestrate the sequence of events: bending down, grabbing the laces, tying the knots. Neurodegenerative diseases like Parkinson’s damage the dopamine-releasing neurons, impairing a person’s ability to execute a series of commands. For example, if you ask Parkinson’s patients to draw a V shape, they might draw the line going down just fine or the line going up just fine. But they have major difficulty making the switch from one direction to the other, and spend much longer at the transition. Before researchers can develop targeted therapies for such diseases, they need to understand exactly what the function of dopamine is at a fundamental neurological level in normal brains.

    Jin’s team designed a study in which mice chose between pressing one of two levers to get a sugary treat. The levers were on the right and left side of a custom-built chamber, with the treat dispenser in the middle. The levers retracted from the chamber at the start of each trial and reappeared after either two seconds or eight seconds. The mice quickly learned that when the levers reappeared after the shorter time, pressing the left lever yielded a treat. When they reappeared after the longer time, pressing the right lever resulted in a treat. Thus, the two sides represented a simplified two-choice situation for the mice — they moved to the left side of the chamber initially, but if the levers didn’t reappear within a certain amount of time, the mice shifted to the right side based on an internal decision.

    “This particular design allows us to ask a unique question about what happens in the brain during this mental and physical switch from one choice to another,” says Hao Li, a Salk research associate and the paper’s co-first author.

    As the mice performed the trials, the researchers used a technique called fast-scan cyclic voltammetry to measure dopamine concentration in the animals’ brains via embedded electrodes much finer than a human hair. The technique allows for very fine-time-scale measurement (in this study, sampling occurred 10 times per second) and therefore can indicate rapid changes in brain chemistry. The voltammetry results showed that fluctuations in brain dopamine level were tightly associated with the animal’s decision. The scientists were actually able to accurately predict the animal’s upcoming choice of lever based on dopamine concentration alone.

    Interestingly, other mice that got a treat by pressing either lever (so removing the element of choice) experienced a dopamine increase as trials got under way, but in contrast their levels remained above baseline (didn’t fluctuate below baseline) the entire time, indicating dopamine’s evolving role when a choice is involved.

    “We are very excited by these findings because they indicate that dopamine could also be involved in ongoing decision, beyond its well-known role in learning,” adds the paper’s co-first author, Christopher Howard, a Salk research collaborator.

    To verify that dopamine level caused the choice change, rather than just being associated with it, the team used genetic engineering and molecular tools — including activating or inhibiting neurons with light in a technique called optogenetics — to manipulate the animals’ brain dopamine levels in real time. They found they were able to bidirectionally switch mice from one choice of lever to the other by increasing or decreasing dopamine levels.

    Jin says these results suggest that dynamically changing dopamine levels are associated with the ongoing selection of actions. “We think that if we could restore the appropriate dopamine dynamics — in Parkinson’s disease, OCD and drug addiction — people might have better control of their behavior. This is an important step in understanding how to accomplish that.”


  8. Research shows certain genes, in healthy environments, can lengthen lifespan

    May 3, 2016 by Ashley

    From the University at Buffalo media release:

    fitnessResearchers at the University at Buffalo Research Institute on Addictions have discovered how a gene in the brain’s dopamine system can play an important role in prolonging lifespan: it must be coupled with a healthy environment that includes exercise.

    The study, led by Panayotis (Peter) K. Thanos, senior research scientist at RIA, appears in the current, online version of Oncotarget Aging.

    Thanos and his team studied the genes in dopamine to assess their impact on lifespan and behavior in mice. Dopamine is a neurotransmitter that helps control the brain’s reward and pleasure centers and helps regulate physical mobility and emotional response.

    The researchers found that the dopamine D2 receptor gene (D2R) significantly influences lifespan, body weight and locomotor activity, but only when combined with an enriched environment that included social interaction, sensory and cognitive stimulation and, most critically, exercise.

    “The incorporation of exercise is an important component of an enriched environment and its benefits have been shown to be a powerful mediator of brain function and behavior,” Thanos says.

    The mice in the enriched environment lived anywhere from 16 to 22 percent longer than those in a deprived environment, depending on the level of D2R expression.

    “These results provide the first evidence of D2R gene-environment interaction playing an important role in longevity and aging,” Thanos says. “The dichotomy over genes versus environment has provided a rigorous and long debate in deciphering individual differences in longevity. In truth, there exists a complex interaction between the two which contribute to the differences.”

    Research exploring this genetic-environmental interaction should lead to a better understanding and prediction of the potential benefits of specific environments, such as those including exercise, on longevity and health during aging.


  9. Rat study reveals long-term effects of adolescent amphetamine abuse on the brain

    April 5, 2016 by Ashley

    From the University of Illinois at Urbana-Champaign media release:

    addiction pillsA study of rats given regular, high doses of amphetamine finds that those exposed to the drug at an age corresponding to human adolescence experience long-term changes in brain function that persist into adulthood.

    The study, reported in the journal Neuroscience, found that amphetamine leads to changes in dopamine signaling. Dopamine is a neurotransmitter that plays a role in memory, attention, learning and feelings of pleasure.

    “The dopamine system, which continues to develop throughout adolescence and young adulthood, is a primary target of psychostimulant drugs like amphetamine,” said University of Illinois psychology professor Joshua Gulley, who led the new research. “Changes in dopamine function in response to repeated drug exposure are likely to contribute to the behavioral consequences — addiction and relapse, for example — that abusers experience.”

    Parallels between rat and human development make rats a worthy model for the study of human drug addiction, which often begins in adolescence, Gulley said.

    Rats exhibit many of the characteristics that human adolescents do. They tend to be more impulsive than adult rats; they tend to make more risky decisions,” he said. They also can engage in “addiction-like behaviors,” he said.

    They show increased drug use in response to stress,” Gulley said. “And, just as in humans, there is evidence that animals that start using drugs in adolescence are more likely to relapse than animals that start in adulthood.”

    A limitation of the new study was that, unlike humans, who generally choose whether or not to partake in drug use, “the rats had no say in whether they got amphetamine,” Gulley said.

    A previous study from Gulley and his colleagues looked at the effects of amphetamine abuse on working memory — the ability to retain information just long enough to use it — in young and adult rats.

    “In that study, we found that animals that were exposed to the drug during adolescence had much more significant deficits in working memory than those exposed during adulthood,” Gulley said.

    The researchers hypothesized that drug exposure during adolescence, a time of vast changes in the brain, “somehow influences the normal developmental trajectory,” Gulley said. “But how?”

    To get at this question, the team focused on the prefrontal cortex, a brain region behind the forehead that is among the last to fully develop during adolescence. The researchers found that repeated exposure to amphetamine — beginning in adulthood or in adolescence — reduced the ability of key cells in the rats’ prefrontal cortex to respond to dopamine. In this part of the brain, dopamine influences “inhibitory tone,” telling cells to stop responding to a stimulus, Gulley said.

    “Inhibition in the nervous system is just as important as activation,” he said. “You need cells that are firing and communicating with one another, but you also need cells to stop communicating with one another at certain times and become quiet.

    “Our research suggests that a subtype of dopamine receptor, the D1 receptor, is altered following amphetamine exposure,” Gulley said. “It’s either not responding to dopamine or there are not as many of these receptors after exposure as there used to be.”

    This change in dopamine signaling persisted for 14 weeks after exposure to amphetamine in the adolescent-exposed rats, he said.

    “That’s akin to a change in humans that persists from adolescence until sometime in their 30s, long after drug use stopped,” he said.

    “Along with other studies, this shows pretty clear evidence that drug use during adolescence, a time when the brain is still developing, has extremely long-lasting consequences that go far beyond the last drug exposure,” Gulley said.


  10. Study suggests dopamine regulates the motivation to act

    May 17, 2013 by Ashley

    From the Asociacion RUVID press release via MedicalXpress:

    mental healthThe widespread belief that dopamine regulates pleasure could go down in history with the latest research results on the role of this neurotransmitter. Researchers have proved that it regulates motivation, causing individuals to initiate and persevere to obtain something either positive or negative.

    The neuroscience journal Neuron publishes an article by researchers at the Universitat Jaume I of Castellón that reviews the prevailing theory on dopamine and poses a major paradigm shift with applications in diseases related to lack of motivation and mental fatigue and depression, Parkinson’s, multiple sclerosis, fibromyalgia, etc. and diseases where there is excessive motivation and persistence as in the case of addictions.

    “It was believed that dopamine regulated pleasure and reward and that we release it when we obtain something that satisfies us, but in fact the latest scientific evidence shows that this neurotransmitter acts before that, it actually encourages us to act. In other words, dopamine is released in order to achieve something good or to avoid something evil”, explains Mercè Correa.

    Studies had shown that dopamine is released by pleasurable sensations but also by stress, pain or loss. These research results however had been skewed to only highlight the positive influence, according to Correa. The new article is a review of the paradigm based on the data from several investigations, including those conducted over the past two decades by the Castellón group in collaboration with the John Salamone of the University of Connecticut (USA), on the role of dopamine in the motivated behaviour in animals.

    The level of dopamine depends on individuals, so some people are more persistent than others to achieve a goal. “Dopamine leads to maintain the level of activity to achieve what is intended. This in principle is positive, however, it will always depend on the stimuli that are sought: whether the goal is to be a good student or to abuse of drugs” says Correa. High levels of dopamine could also explain the behaviour of the so-called sensation seekers as they are more motivated to act.

    Application for depression and addiction

    To know the neurobiological parameters that make people be motivated by something is important to many areas such as work, education or health. Dopamine is now seen as a core neurotransmitter to address symptoms such as the lack of energy that occurs in diseases such as depression. “Depressed people do not feel like doing anything and that’s because of low dopamine levels,” explains Correa. Lack of energy and motivation is also related to other syndromes with mental fatigue such as Parkinson’s, multiple sclerosis or fibromyalgia, among others.

    In the opposite case, dopamine may be involved in addictive behaviour problems, leading to an attitude of compulsive perseverance. In this sense, Correa indicates that dopamine antagonists which have been applied so far in addiction problems probably have not worked because of inadequate treatments based on a misunderstanding of the function of dopamine.