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What if the Placebo Effect Isn’t a Trick? - The New York Times

The discovery of this genetic correlation to placebo response set Hall off on a continuing effort to identify the biochemical ensemble she calls the placebome — the term reflecting her belief that it will one day take its place among the other important “-omes” of medical science, from the genome to the microbiome. The rs4680 gene snippet is one of a group that governs the production of COMT, and COMT is one of a number of enzymes that determine levels of catecholamines, a group of brain chemicals that includes dopamine and epinephrine. (Low COMT tends to mean higher levels of dopamine, and vice versa.) Hall points out that the catecholamines are associated with stress, as well as with reward and good feeling, which bolsters the possibility that the placebome plays an important role in illness and health, especially in the chronic, stress-related conditions that are most susceptible to placebo effects.

Dopamine Drives Early Addiction to Heroin - Neuroscience News

To prove that increased dopamine directly causes drug reinforcement, the team looked at the effects of silencing dopamine in mice with a well-established heroin addiction and were consistently self-administering the drug using a lever. They found that when they silenced the dopamine neurons, the mice were much less likely to self-administer heroin. Crucially, when they did this early in the addiction phase, the mice were less likely to develop the habit of self-administering heroin. This showed that activation of dopamine neurons in the nucleus accumbens is required for the early positive reinforcing effects of opioid drugs.

Just a few drinks can change how memories are formed -- ScienceDaily

One of the downstream dominos in the signaling pathway affected by alcohol is a gene called dopamine-2-like receptor, which makes a protein on neurons that recognizes dopamine, the "feel-good" neurotransmitter. "The dopamine-2-like receptor is known to be involved in encoding whether a memory is pleasing or aversive," Petruccelli said. And alcohol hijacks this conserved memory pathway to form cravings. In the case of the alcohol reward pathway studied, the signaling cascade didn't turn the dopamine receptor gene on or off, or increase or decrease the amount of protein made, Kaun said. Instead, it had a subtler effect -- it changed the version of the protein made by a single amino acid "letter" in an important area. "We don't know what the biological consequences of that small change are, but one of the important findings from this study is that scientists need to look not only at which genes are being turned on and off, but which forms of each gene are getting turned on and off," Kaun said. "We think these results are highly likely to translate to other forms of addiction, but nobody has investigated that."

New target of alcohol in the brain -- ScienceDaily

"The KCNK13 channel is absolutely required for alcohol to stimulate the release of dopamine by these neurons," said Mark Brodie, professor of physiology and biophysics in the UIC College of Medicine and lead author of the study. "Without the channel, alcohol can't stimulate the release of dopamine, and so drinking is likely less rewarding. We think that the KCNK13 channel presents an extremely exciting new target for drugs that could potentially help people with alcohol use disorder to stop drinking."

Dads' Nicotine Use May Cause Cognitive Problems for Children and Grandchildren - Neuroscience News

Analysis of spermatozoa from the original nicotine-exposed males indicated that promoter regions of multiple genes had been epigenetically modified, including the dopamine D2 gene, critical for brain development and learning, suggesting that these modifications likely contributed to the cognitive deficits in the descendants.

Connection Between Dopamine and Behavior Related to Pain and Fear - Neuroscience News

The researchers subjected the animals to small electric shocks, but also taught the animals how to escape the shocks by pressing a small lever. Using optogenetics, they controlled the amount of dopamine released by neurons in the nucleus accumbens. Animals with high levels of dopamine in this brain region learned to avoid a shock more quickly and more often than animals that had a lower level of dopamine in this region.

Running } endocannabinoids } dopamine } motivation?

The researchers also examined the role that endocannabinoids play in this process. Endocannabinoids, brain chemicals that resemble the active ingredients in marijuana, play key roles in many brain processes. Here, Dr. Cheer and his colleagues found that endocannabinoids essentially open the gate that allows the dopamine neurons to fire. When the researchers reduced the level of endocannabinoids, the animals were much less likely to move to avoid shocks.

Exercise Can Help Beat Cocaine Addiction - Neuroscience News

Using animal models, Thanos found that regular aerobic exercise (one hour on a treadmill, five times a week) decreased stress-induced cocaine-seeking behavior. Exercise also altered behavioral and physiological responses to stress. Individuals who are addicted to cocaine have altered neural, behavioral and physiological responses to stress. Recent research by Thanos demonstrated how exercise can alter the brain’s mesolimbic dopamine pathway, which is linked to the rewarding and reinforcing properties of drugs such as cocaine. In addition, exercise has been shown to reduce stress hormones and elevate mood, which could assist in alleviating anxiety and negative emotions associated with withdrawal.

Reward and unease are closely linked in the brain -- ScienceDaily

One of the key components of the reward system is the signal substance dopamine, which acts as a chemical messenger between nerve cells. Dopamine stimulates motivation and causes animals and humans to exert themselves to achieve anything that is experienced as rewarding. When the researchers examined the dopamine-based signalling in the brain, they saw that the dopamine level in normal mice fell in the reward centre of the brain when the animals experienced something unpleasant. In contrast, it increased slightly in the mice that lacked melanocortin 4 receptors. "It seems that this receptor in some way prevents danger signals from activating the reward system. If the receptor is missing, the danger signals will gain access to the reward system and activate it. This means that mice that lack the receptor will seek out things that are associated with danger or discomfort," says David Engblom.

Why folks coming off stimulants have panic attacks

After conditioning rats to associate a specific sound (think of it as their Jaws music) with an aversive experience (a mild footshock), the team then began the extinction process. As expected, when the sound was played many times without the footshock, rats stopped behaving as if they were afraid of the sound. However, when VTA dopamine neurons were silenced just after playing the sound -- exactly when the rats expected their feet to be shocked -- they could not unlearn the fear response. This showed that without VTA dopamine activity at that specific time, the mental link between the sound and the shock could not be removed.

Google’s DeepMind is using AI to explore dopamine’s role in learning

In animals, dopamine is believed to reinforce behaviors by strengthening synaptic links in the prefrontal cortex. But the consistency of the neural network’s behavior suggests that dopamine also conveys and encodes information about tasks and rule structures, according to the researchers.

Rare mutation of gene carried by Quebec family gives insight into how the brain is wired: Brain scans could further understanding of psychiatric disorders, brain's reward system -- ScienceDaily

By scanning the brain of 20 family members who share an altered copy of DCC, the researchers found less connectivity between the areas where dopamine neurons originate (the substantia nigra and ventral tegmental area) and their target sites, such as the striatum and frontal cortex. One of these target sites -- the striatum -- was also smaller. "It's very interesting because we were able to show that this DCC gene alteration induces similar changes to the brain in both mice and humans," says Cecilia Flores. Because the brain systems affected by the gene influence responses to rewards, it was not surprising to see that the family members with the DCC mutation also have lower impulsivity traits and are less likely to smoke cigarettes. Indeed, an increasing number of studies, including those by Professor Flores' team, link DCC to psychiatric conditions. "Because the gene affects the brain's dopamine pathways, which are implicated in schizophrenia, addiction and depression, our study potentially helps us understand how these disorders arise.

Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction

Exercised rats had 18% and 21% lower D1R-like binding levels compared to sedentary rats within the olfactory tubercle (OT) and nucleus accumbens shell (AcbS), respectively. In addition, male and female exercise rats showed greater D2R-like binding levels within the dorsomedial (DM CPu; 30%), ventrolateral (VL CPu; 24%), and ventromedial (VM CPu; 27%) caudate putamen, as well as the OT (19%). Greater D2R-like binding in the nucleus accumbens core (AcbC; 24%) and shell (AcbS; 25%) of exercised rats compared to sedentary rats approached significance. No effects were found for DAT binding.

Acupuncture alters key neurotransmitters

Steffensen is going beyond the previous claims and is studying the neuroscience behind acupuncture. He has shown it to be an effective method of activating pathways from the peripheral nervous system to the central nervous system. Here's how: Those suffering from withdrawal have dysregulated dopamine levels in the midbrain reward/pleasure system This causes dysregulation of GABA neurons in this system, and they become hyperactive, inhibiting dopamine neurons and lowering dopamine levels during withdrawl Lowered dopamine levels is the driving force for relapse Accupuncture stimulation inhibits GABA neurons This restores dopamine levels and effectively lowers the driving force for relapse

How Dopamine Neurons Contribute to Memory Formation in Humans - Neuroscience News

“What we discovered was that a subset of the dopaminergic neurons responded only when an image was novel, but not when it was familiar. In other words, it indicated if the image was new, but not if something was familiar,” said Jan Kaminski, PhD, first author of the study and a project scientist at Cedars-Sinai. “This is an important new scientific discovery, because it has so far remained unclear how the dopaminergic system contributes to episodic memory formation.”

Brain activity linked to stress changes chemical codes: Findings may be relevant to other disorders, from autism to PTSD -- ScienceDaily

In the new findings, the researchers studied the change in neurotransmitter identity when rats, which are nocturnal, are exposed to long day lengths. This exposure led to elevated activity of paraventricular (PaVN) neurons in the hypothalamus and by consequence a loss in their expression of dopamine, a neurotransmitter that is linked with many aspects of normal behavior. When the researchers suppressed the elevation of activity that resulted from the long-day exposure, exclusively in the PaVN neurons, they blocked the transmitter switch that would have occurred under these normal light conditions.

One Sleepless Night Increases Dopamine in the Human Brain

“This is the first time that a study provides evidence that in the human brain, dopamine is involved in the adaptations that result from sleep deprivation,” said Nora Volkow, MD, director of the National Institute on Drug Abuse, who led the study. Volkow and colleagues found that in healthy participants, sleep deprivation increased dopamine in two brain structures: the striatum, which is involved in motivation and reward, and the thalamus, which is involved in alertness. The researchers also found that the amount of dopamine in the brain correlated with feelings of fatigue and impaired performance on cognitive tasks. “These findings suggest dopamine may increase after sleep deprivation as a compensatory response to the effects of increased sleep drive in the brain,” said David Dinges, PhD, at the University of Pennsylvania School of Medicine, an expert unaffiliated with the study. “The extent to which this occurs may differentiate how vulnerable people are to the neurobehavioral effects of sleep loss,” Dinges said.

Drug-Induced Psychosis: How to Avoid Star Gazing in Schizophrenia Research by Looking at More Obvious Sources of Light

They administered dextroamphetamine by mouth on days 1, 3, and 5 to 10 healthy volunteers, and measured the effect on striatal dopamine release before exposure, then the day of first exposure, then 2 weeks later after the third dose, using the PET/[11C] raclopride technique. Each dose of amphetamine caused greater dopamine release in the ventral striatum together with greater behavioral responses. Indeed, 1 year later there was a greater psychomotor response and greater increase dopamine release compared to the initial dose, in the ventral striatum, progressively extending to the dorsal caudate and putamen (Boileau et al., 2006). Such findings have led to the “dopamine sensitization” hypothesis of schizophrenia which postulates that a sensitized dopamine system is responsible for the genesis of psychotic symptoms (Peleg-Raibstein et al., 2009).

How Meth Destroys The Body | The Meth Epidemic | FRONTLINE | PBS

"There [are] a whole variety of reasons to try methamphetamine," explains Dr. Richard Rawson, associate director of UCLA's Integrated Substance Abuse Programs. "[H]owever, once they take the drug … their reasons are pretty much the same: They like how it affects their brain[s]." Meth users have described this feeling as a sudden rush of pleasure lasting for several minutes, followed by a euphoric high that lasts between six and 12 hours, and it is the result of drug causing the brain to release excessive amounts of the chemical dopamine, a neurotransmitter that controls pleasure. All drugs of abuse cause the release of dopamine, even alcohol and nicotine, explains Rawson, "[But] methamphetamine produces the mother of all dopamine releases." For example, in lab experiments done on animals, sex causes dopamine levels to jump from 100 to 200 units, and cocaine causes them to spike to 350 units. "[With] methamphetamine you get a release from the base level to about 1,250 units, something that's about 12 times as much of a release of dopamine as you get from food and sex and other pleasurable activities," Rawson says. "This really doesn't occur from any normally rewarding activity. That's one of the reasons why people, when they take methamphetamine, report having this euphoric [feeling] that's unlike anything they've ever experienced." Then, when the drug wears off, users experience profound depression and feel the need to keep taking the drug to avoid the crash.

Link between hallucinations and dopamine not such a mystery, finds study -- ScienceDaily

"Our brain uses prior experiences to generate sensory expectations that help fill in the gaps when sounds or images are distorted or unclear," said Guillermo Horga, MD, PhD, assistant professor of clinical psychiatry at CUIMC and a research psychiatrist at NYSPI. "In individuals with schizophrenia, this process appears to be altered, leading to extreme perceptual distortions, such as hearing voices that are not there. Furthermore, while such hallucinations are often successfully treated by antipsychotic drugs that block the neurotransmitter dopamine in a brain structure known as the striatum, the reason for this has been a mystery since this neurotransmitter and brain region are not typically associated with sensory processing." The researchers designed an experiment that induces an auditory illusion in both healthy participants and participants with schizophrenia. They examined how building up or breaking down sensory expectations can modify the strength of this illusion. They also measured dopamine release before and after administering a drug that stimulates the release of dopamine. Patients with hallucinations tended to perceive sounds in a way that was more similar to what they had been cued to expect, even when sensory expectations were less reliable and illusions weakened in healthy participants. This tendency to inflexibly hear what was expected was worsened after giving a dopamine-releasing drug, and more pronounced in participants with elevated dopamine release, and more apparent in participants with a smaller dorsal anterior cingulate (a brain region previously shown to track reliability of environmental cues).

Body movements just need a 'puff' of dopamine to get started: A new study in mice suggests that a burst of dopamine levels at the beginning of a movement only, as opposed to all the time, is what gets us going; this may have important implications for treating Parkinson's disease -- ScienceDaily

Experts have long worked to understand why the absence of these so-called dopaminergic neurons (and therefore, the lack of dopamine) leads to the motor dysfunctions that are the hallmarks Parkinson's, such as stiffness, slow movements and tremors. The more widely accepted explanation has been that, in order to move normally, our brain constantly needs a certain level of dopamine -- something that Parkinson's patients progressively lose. However, as psychiatrist and neuroscientist Joaquim Alves da Silva, first author of the new study, explains, people with Parkinson's disease actually "do not have a global motor problem." As incredible as it may seem, they can even ride a bicycle -- a rather complex motor task -- if pushed at the right time. The motor problems that Parkinson's patients experience are more specific, and this was the observation that motivated the new study. "The patients' problem is in the difficulty to initiate movement and in the slowness of movement," adds Alves da Silva. In fact, as these authors now showed in mice not afflicted by Parkinson's disease, for a movement to unfold correctly it only takes a "puff" of dopamine -- or more precisely, a peak of dopaminergic cell activity -- right before the movements starts. In other words, dopamine (or, in this case, the activity of the cells that produce it) is just a "trigger" for voluntary movements. "Our most important result is that we showed, for the first time, that the change in neural activity is necessary to promote movement," says Alves da Silva. "And also for the first time, we showed that the dopamine peak that precedes movement initiation does not only regulate initiation, but also regulates movement vigor."

Low Dopamine Levels During Withdrawal Promote Relapse to Smoking

“This study is an elegant example of yet another way that addiction ‘hijacks’ the reward system. The phasic release of dopamine triggers us to seek things that, in theory, help us to adapt to our environment,” commented Dr. John Krystal, editor of Biological Psychiatry. “However, in addiction the phasic release of dopamine is heightened and it triggers the pursuit of abused substances. This disturbance of dopamine function would, conceivably, make it that much harder to avoid seeking drugs of abuse.”

Key psychiatric drug target comes into focus: Team determines first high-resolution structure of dopamine receptor -- ScienceDaily

One way or another, many psychiatric drugs work by binding to receptor molecules in the brain that are sensitive to the neurotransmitter dopamine, a chemical signal that is central to how our experiences shape our behavior. But because scientists still don't understand the differences between the many kinds of dopamine receptors present on brain cells, most of these drugs are "messy," binding to multiple different dopamine receptor molecules and leading to serious side effects ranging from movement disorders to pathological gambling.

Surprising discovery about how neurons talk to each other -- ScienceDaily

The team then demonstrated that the increase in acidity was driven by a transport channel in the cell's surface, which allowed an influx of negatively charged glutamate ions to enter the neuron, thus increasing its acidity. Genetically removing the transporter in fruit flies and mice made the animals less responsive to amphetamine, a drug that exerts its effect by stimulating dopamine release from neurons. "In this case, glutamate is not acting as a neurotransmitter. Instead it is functioning primarily as a source of negative charge, which is being used by these vesicles in a really clever way to manipulate vesicle acidity and therefore change their dopamine content," Freyberg said. "This calls into question the whole textbook model of vesicles as having fixed amounts of single neurotransmitters. It appears that these vesicles contain both dopamine and glutamate, and dynamically modify their content to match the conditions of the cell as needed."

Sleep, dopamine and memory

The study shows that increasing sleep, with either a sleep-promoting drug or by genetic stimulation of the neural sleep circuit, decreases signaling activity by dopamine, while at the same time enhancing memory retention. Conversely, increasing arousal stimulates dopamine signaling and accelerates forgetting. This signal activity isn’t constant but is tied directly to the animal’s arousal level. “Our findings add compelling evidence to support the model that sleep reduces the forgetting signal in the brain, thereby keeping memories intact,” Davis said. “As sleep progresses to deeper levels, dopamine neurons become less reactive to stimuli and this leads to more stable memories.

Dopamine toggling governs decision making

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."