Posts tagged dopamine
Articles and news from the latest research reports.
This Is How Your Brain Becomes Addicted to Caffeine
Within 24 hours of quitting the drug, your withdrawal symptoms begin. Initially, they’re subtle: The first thing you notice is that you feel mentally foggy, and lack alertness. Your muscles are fatigued, even when you haven’t done anything strenuous, and you suspect that you’re more irritable than usual.
Over time, an unmistakable throbbing headache sets in, making it difficult to concentrate on anything. Eventually, as your body protests having the drug taken away, you might even feel dull muscle pains, nausea and other flu-like symptoms.
This isn’t heroin, tobacco or even alcohol withdrawl. We’re talking about quitting caffeine, a substance consumed so widely (the FDA reports thatmore than 80 percent of American adults drink it daily) and in such mundane settings (say, at an office meeting or in your car) that we often forget it’s a drug—and by far the world’s most popular psychoactive one.
Like many drugs, caffeine is chemically addictive, a fact that scientists established back in 1994. This past May, with the publication of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM), caffeine withdrawal was finally included as a mental disorder for the first time—even though its merits for inclusion are symptoms that regular coffee-drinkers have long known well from the times they’ve gone off it for a day or more.
Why, exactly, is caffeine addictive? The reason stems from the way the drug affects the human brain, producing the alert feeling that caffeine drinkers crave.
Soon after you drink (or eat) something containing caffeine, it’s absorbed through the small intestine and dissolved into the bloodstream. Because the chemical is both water- and fat-soluble (meaning that it can dissolve in water-based solutions—think blood—as well as fat-based substances, such as our cell membranes), it’s able to penetrate the blood-brain barrier and enter the brain.
Structurally, caffeine closely resembles a molecule that’s naturally present in our brain, called adenosine (which is a byproduct of many cellular processes, including cellular respiration)—so much so, in fact, that caffeine can fit neatly into our brain cells’ receptors for adenosine, effectively blocking them off. Normally, the adenosine produced over time locks into these receptors and produces a feeling of tiredness.
When caffeine molecules are blocking those receptors, they prevent this from occurring, thereby generating a sense of alertness and energy for a few hours. Additionally, some of the brain’s own natural stimulants (such as dopamine) work more effectively when the adenosine receptors are blocked, and all the surplus adenosine floating around in the brain cues the adrenal glands to secrete adrenaline, another stimulant.
For this reason, caffeine isn’t technically a stimulant on its own, says Stephen R. Braun, the author or Buzzed: the Science and Lore of Caffeine and Alcohol, but a stimulant enabler: a substance that lets our natural stimulants run wild. Ingesting caffeine, he writes, is akin to “putting a block of wood under one of the brain’s primary brake pedals.” This block stays in place for anywhere from four to six hours, depending on the person’s age, size and other factors, until the caffeine is eventually metabolized by the body.
In people who take advantage of this process on a daily basis (i.e. coffee/tea, soda or energy drink addicts), the brain’s chemistry and physical characteristics actually change over time as a result. The most notable change is that brain cells grow more adenosine receptors, which is the brain’s attempt to maintain equilibrium in the face of a constant onslaught of caffeine, with its adenosine receptors so regularly plugged (studies indicate that the brain also responds by decreasing the number of receptors for norepinephrine, a stimulant). This explains why regular coffee drinkers build up a tolerance over time—because you have more adenosine receptors, it takes more caffeine to block a significant proportion of them and achieve the desired effect.
This also explains why suddenly giving up caffeine entirely can trigger a range of withdrawal effects. The underlying chemistry is complex and not fully understood, but the principle is that your brain is used to operating in one set of conditions (with an artificially-inflated number of adenosine receptors, and a decreased number of norepinephrine receptors) that depend upon regular ingestion of caffeine. Suddenly, without the drug, the altered brain chemistry causes all sorts of problems, including the dreaded caffeine withdrawal headache.
The good news is that, compared to many drug addictions, the effects are relatively short-term. To kick the thing, you only need to get through about 7-12 days of symptoms without drinking any caffeine. During that period, your brain will naturally decrease the number of adenosine receptors on each cell, responding to the sudden lack of caffeine ingestion. If you can make it that long without a cup of joe or a spot of tea, the levels of adenosine receptors in your brain reset to their baseline levels, and your addiction will be broken.
MIT researchers reveal how the brain keeps eyes on the prize.
“Are we there yet?”
As anyone who has traveled with young children knows, maintaining focus on distant goals can be a challenge. A new study from MIT suggests how the brain achieves this task, and indicates that the neurotransmitter dopamine may signal the value of long-term rewards. The findings may also explain why patients with Parkinson’s disease — in which dopamine signaling is impaired — often have difficulty in sustaining motivation to finish tasks.
The work is described this week in the journal Nature.
Previous studies have linked dopamine to rewards, and have shown that dopamine neurons show brief bursts of activity when animals receive an unexpected reward. These dopamine signals are believed to be important for reinforcement learning, the process by which an animal learns to perform actions that lead to reward.
Taking the long view
In most studies, that reward has been delivered within a few seconds. In real life, though, gratification is not always immediate: Animals must often travel in search of food, and must maintain motivation for a distant goal while also responding to more immediate cues. The same is true for humans: A driver on a long road trip must remain focused on reaching a final destination while also reacting to traffic, stopping for snacks, and entertaining children in the back seat.
The MIT team, led by Institute Professor Ann Graybiel — who is also an investigator at MIT’s McGovern Institute for Brain Research — decided to study how dopamine changes during a maze task approximating work for delayed gratification. The researchers trained rats to navigate a maze to reach a reward. During each trial a rat would hear a tone instructing it to turn either right or left at an intersection to find a chocolate milk reward.
Rather than simply measuring the activity of dopamine-containing neurons, the MIT researchers wanted to measure how much dopamine was released in the striatum, a brain structure known to be important in reinforcement learning. They teamed up with Paul Phillips of the University of Washington, who has developed a technology called fast-scan cyclic voltammetry (FSCV) in which tiny, implanted, carbon-fiber electrodes allow continuous measurements of dopamine concentration based on its electrochemical fingerprint.
“We adapted the FSCV method so that we could measure dopamine at up to four different sites in the brain simultaneously, as animals moved freely through the maze,” explains first author Mark Howe, a former graduate student with Graybiel who is now a postdoc in the Department of Neurobiology at Northwestern University. “Each probe measures the concentration of extracellular dopamine within a tiny volume of brain tissue, and probably reflects the activity of thousands of nerve terminals.”
Gradual increase in dopamine
From previous work, the researchers expected that they might see pulses of dopamine released at different times in the trial, “but in fact we found something much more surprising,” Graybiel says: The level of dopamine increased steadily throughout each trial, peaking as the animal approached its goal — as if in anticipation of a reward.
The rats’ behavior varied from trial to trial — some runs were faster than others, and sometimes the animals would stop briefly — but the dopamine signal did not vary with running speed or trial duration. Nor did it depend on the probability of getting a reward, something that had been suggested by previous studies.
“Instead, the dopamine signal seems to reflect how far away the rat is from its goal,” Graybiel explains. “The closer it gets, the stronger the signal becomes.” The researchers also found that the size of the signal was related to the size of the expected reward: When rats were trained to anticipate a larger gulp of chocolate milk, the dopamine signal rose more steeply to a higher final concentration.
In some trials the T-shaped maze was extended to a more complex shape, requiring animals to run further and to make extra turns before reaching a reward. During these trials, the dopamine signal ramped up more gradually, eventually reaching the same level as in the shorter maze. “It’s as if the animal were adjusting its expectations, knowing that it had further to go,” Graybiel says.
An ‘internal guidance system’
“This means that dopamine levels could be used to help an animal make choices on the way to the goal and to estimate the distance to the goal,” says Terrence Sejnowski of the Salk Institute, a computational neuroscientist who is familiar with the findings but who was not involved with the study. “This ‘internal guidance system’ could also be useful for humans, who also have to make choices along the way to what may be a distant goal.”
One question that Graybiel hopes to examine in future research is how the signal arises within the brain. Rats and other animals form cognitive maps of their spatial environment, with so-called “place cells” that are active when the animal is in a specific location. “As our rats run the maze repeatedly,” she says, “we suspect they learn to associate each point in the maze with its distance from the reward that they experienced on previous runs.”
As for the relevance of this research to humans, Graybiel says, “I’d be shocked if something similar were not happening in our own brains.” It’s known that Parkinson’s patients, in whom dopamine signaling is impaired, often appear to be apathetic, and have difficulty in sustaining motivation to complete a long task. “Maybe that’s because they can’t produce this slow ramping dopamine signal,” Graybiel says.
New Findings Could Help Improve Development of Drugs for Addiction
Scientists from the Florida campus of The Scripps Research Institute have described findings that could enable the development of more effective drugs for addiction with fewer side effects.
The study, published in the August 2, 2013 issue of the Journal of Biological Chemistry, showed in a combination of cell and animal studies that one active compound maintains a strong bias towards a single biological pathway, providing insight into what future drugs could look like.
The compound examined in the study, known as 6’- guanidinonaltrindole (6’-GNTI), targets the kappa opioid receptor (KOR). Located on nerve cells, KOR plays a role in the release of dopamine, a neurotransmitter that plays a key role in drug addiction. Drugs of abuse often cause the brain to release large amounts of dopamine, flooding the brain’s reward system and reinforcing the addictive cycle.
“There are a number of drug discovery efforts ongoing for KOR,” said Laura Bohn, a TSRI associate professor, who led the study. “The ultimate question is how this receptor should be acted upon to achieve the best therapeutic effects. Our study identifies a marker that shows how things normally happen in live neurons—a critically important secondary test to evaluate potential compounds.”
While KOR has become the focus for drug discovery efforts aimed at treating addiction and mood disorders, KOR can react to signals that originate independently from multiple biological pathways, so current drug candidates targeting KOR often produce unwanted side effects. Compounds that activate KOR can decrease the rewarding effects of abused drugs, but also induce sedation and depression.
The new findings, from studies of nerve cells in the striatum (an area of the brain involved in motor activity and higher brain function), reveal a point on the KOR signaling pathway that may prove to be an important indicator of whether drug candidates can produce effects similar to the natural biological effects.
“Standard screening assays can catch differences but those differences may not play out in live tissue,” Bohn noted. “Essentially, we have shown an important link between cell-based screening assays and what occurs naturally in animal models.”
(Source: scripps.edu)
Alcoholism Could Be Linked to a Hyper-Active Brain Dopamine System
Those vulnerable to alcoholism may experience an unusually large response in the brain’s reward-seeking pathway when they take a drink
Research from McGill University suggests that people who are vulnerable to developing alcoholism exhibit a distinctive brain response when drinking alcohol, according to a new study by Prof. Marco Leyton, of McGill University’s Department of Psychiatry. Compared to people at low risk for alcohol-use problems, those at high risk showed a greater dopamine response in a brain pathway that increases desire for rewards. These findings, published in the journal Alcoholism: Clinical & Experimental Research, could help shed light on why some people are more at risk of suffering from alcoholism and could mark an important step toward the development of treatment options.
“There is accumulating evidence that there are multiple pathways to alcoholism, each associated with a distinct set of personality traits and neurobiological features”, said Prof. Leyton, a researcher in the Mental Illness and Addiction axis at the Research Institute of the McGill University Health Centre (RI-MUHC). “These individual differences likely influence a wide range of behaviors, both positive and problematic. Our study suggests that a tendency to experience a large dopamine response when drinking alcohol might contribute to one (or more) of these pathways.”
For the study, researchers recruited 26 healthy social drinkers (18 men, 8 women), 18 to 30 years of age, from the Montreal area. The higher-risk subjects were then identified based on personality traits and having a lower intoxication response to alcohol (they did not feel as drunk despite having drunk the same amount). Finally, each participant underwent two positron emission tomography (PET) brain scan exams after drinking either juice or alcohol (about 3 drinks in 15 minutes).
“We found that people vulnerable to developing alcoholism experienced an unusually large brain dopamine response when they took a drink,” said Leyton. “This large response might energize reward-seeking behaviors and counteract the sedative effects of alcohol. Conversely, people who experience minimal dopamine release when they drink might find the sedative effects of alcohol especially pronounced.”
“Although preliminary, the results are compelling,” said Dr. Leyton. “A much larger body of research has identified a role for dopamine in reward-seeking behaviors in general. For example, in both laboratory animals and people, increased dopamine transmission seems to enhance the attractiveness of reward-related stimuli. This effect likely contributes to why having one drink increases the probability of getting a second one – the alcohol-induced dopamine response makes the second drink look all the more desirable. If some people are experiencing unusually large dopamine responses to alcohol, this might put them at risk.”
“People with loved ones struggling with alcoholism often want to know two things: How did they develop this problem? And what can be done to help? Our study helps us answer the first question by furthering our understanding of the causes of addictions. This is an important step toward developing treatments and preventing the disorder in others.”
(Source: newswise.com)
2 dimensions of value: Dopamine neurons represent reward but not aversiveness
To make decisions, we need to estimate the value of sensory stimuli and motor actions, their “goodness” and “badness.” We can imagine that good and bad are two ends of a single continuum, or dimension, of value. This would be analogous to the single dimension of light intensity, which ranges from dark on one end to bright light on the other, with many shades of gray in between. Past models of behavior and learning have been based on a single continuum of value, and it has been proposed that a particular group of neurons (brain cells) that use dopamine as a neurotransmitter (chemical messenger) represent the single dimension of value, signaling both good and bad.
The experiments reported here show that dopamine neurons are sensitive to the value of reward but not punishment (like the aversiveness of a bitter taste). This demonstrates that reward and aversiveness are represented as two discrete dimensions (or categories) in the brain. “Reward” refers to the category of good things (food, water, sex, money, etc.), and “punishment” to the category of bad things (stimuli associated with harm to the body and that cause pain or other unpleasant sensations or emotions).
Rather than having one neurotransmitter (dopamine) to represent a single dimension of value, the present results imply the existence of four neurotransmitters to represent two dimensions of value. Dopamine signals evidence for reward (“gains”) and some other neurotransmitter presumably signals evidence against reward (“losses”). Likewise, there should be a neurotransmitter for evidence of danger and another for evidence of safety. It is interesting that there are three other neurotransmitters that are analogous to dopamine in many respects (serotonin, norepinephrine, and acetylcholine), and it is possible that they could represent the other three value signals.
New Insight Into How Brain ‘Learns’ Cocaine Addiction
A team of researchers says it has solved the longstanding puzzle of why a key protein linked to learning is also needed to become addicted to cocaine. Results of the study, published in the Aug. 1 issue of the journal Cell, describe how the learning-related protein works with other proteins to forge new pathways in the brain in response to a drug-induced rush of the “pleasure” molecule dopamine. By adding important detail to the process of addiction, the researchers, led by a group at Johns Hopkins, say the work may point the way to new treatments.
“The broad question was why and how cocaine strengthened certain circuits in the brain long term, effectively re-wiring the brain for addiction,” says Paul Worley, M.D., a professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine. “What we found in this study was how two very different types of systems in the brain work together to make that happen.” Cocaine addiction, experts say, is among the strongest of addictions.
Worley did not come to the problem as an addiction researcher, but as an expert in a group of genes known as immediate early genes, which rapidly ramp up production in neurons when the brain is exposed to new information. In 2001, he said, a European group led by François Conquet of GlaxoSmithKline reported that deleting mGluR5, a protein complex that responds to the common brain-signaling molecule glutamate, made mice unresponsive to cocaine. “That finding came out of the blue,” says Worley, who knew mGluR proteins for their interactions with immediate early genes. “I never would have thought this type of protein was linked to dopamine and addiction, because the functions for it that we knew about up to that point were completely unrelated. That’s what scientists love: when you’re pretty sure something is right, but you don’t have a clue why.”
The finding set Worley’s research group on a long search for an explanation. Eventually, in addition to studying the effects of altering genes for the relevant proteins in mice, they partnered with experts in measuring the brain’s electrical signals and in a biophysical technique that detects when chemical bonds are rotated within protein molecules. Using different types of experiments, they pieced together a complex story of how dopamine released in response to cocaine works together with mGluR5 and immediate early genes to switch cells into synapse-strengthening mode.
“The process we identified explains how cocaine exposure can co-opt normal mechanisms of learning to induce addiction,” Worley says. Knowing the details of the mechanism may help researchers identify targets for potential drugs to treat addiction, he adds.
(Image: Milos Jokic)
Scientists Find a Potential Cause of Parkinson’s Disease that Points to a New Therapeutic Strategy
Biologists at The Scripps Research Institute (TSRI) have made a significant discovery that could lead to a new therapeutic strategy for Parkinson’s disease.
The findings, recently published online ahead of print in the journal Molecular and Cell Biology, focus on an enzyme known as parkin, whose absence causes an early-onset form of Parkinson’s disease. Precisely how the loss of this enzyme leads to the deaths of neurons has been unclear. But the TSRI researchers showed that parkin’s loss sharply reduces the level of another protein that normally helps protect neurons from stress.
“We now have a good model for how parkin loss can lead to the deaths of neurons under stress,” said TSRI Professor Steven I. Reed, who was senior author of the new study. “This also suggests a therapeutic strategy that might work against Parkinson’s and other neurodegenerative diseases.”
Genetic Clues
Parkinson’s is the world’s second-most common neurodegenerative disease, affecting about one million people in the United States alone. The disease is usually diagnosed after the appearance of the characteristic motor symptoms, which include tremor, muscle rigidity and slowness of movements. These symptoms are caused by the loss of neurons in the substantia nigra, a brain region that normally supplies the neurotransmitter dopamine to other regions that regulate muscle movements.
Most cases of Parkinson’s are considered “sporadic” and are thought to be caused by a variable mix of factors including advanced age, subtle genetic influences, chronic neuroinflammation and exposure to pesticides and other toxins. But between 5 and 15 percent of cases arise specifically from inherited gene mutations. Among these, mutations to the parkin gene are relatively common. Patients who have no functional parkin gene typically develop Parkinson’s-like symptoms before age 40.
Parkin belongs to a family of enzymes called ubiquitin ligases, whose main function is to regulate the levels of other proteins. They do so principally by “tagging” their protein targets with ubiquitin molecules, thus marking them for disposal by roving protein-breakers in cells known as proteasomes. Because parkin is a ubiquitin ligase, researchers have assumed that its absence allows some other protein or proteins to evade proteasomal destruction and thus accumulate abnormally and harm neurons. But since 1998, when parkin mutations were first identified as a cause of early-onset Parkinson’s, consensus about the identity of this protein culprit has been elusive.
“There have been a lot of theories, but no one has come up with a truly satisfactory answer,” Reed said.
Oxidative Stress
In 2005, Reed and his postdoctoral research associate (and wife) Susanna Ekholm-Reed decided to investigate a report that parkin associates with another ubiquitin ligase known as Fbw7. “We soon discovered that parkin regulates Fbw7 levels by tagging it with ubiquitin and thus targeting it for degradation by the proteasome,” said Ekholm-Reed.
Loss of parkin, they found, leads to rises in Fbw7 levels, specifically for a form of the protein known as Fbw7β. The scientists observed these elevated levels of Fbw7β in embryonic mouse neurons from which parkin had been deleted, in transgenic mice that were born without the parkin gene, and even in autopsied brain tissue from Parkinson’s patients who had parkin mutations.
Subsequent experiments showed that when neurons are exposed to harmful molecules known as reactive oxygen species, parkin appears to work harder at tagging Fbw7β for destruction, so that Fbw7β levels fall. Without the parkin-driven decrease in Fbw7β levels, the neurons become more sensitive to this “oxidative stress”—so that more of them undergo a programmed self-destruction called apoptosis. Oxidative stress, to which dopamine-producing substantia nigra neurons may be particularly vulnerable, has long been considered a likely contributor to Parkinson’s.
“We realized that there must be a downstream target of Fbw7β that’s important for neuronal survival during oxidative stress,” said Ekholm-Reed.
A New Neuroprotective Strategy
The research slowed for a period due to a lack of funding. But then, in 2011, came a breakthrough. Other researchers who were investigating Fbw7’s role in cancer reported that it normally tags a cell-survival protein called Mcl-1 for destruction. The loss of Fbw7 leads to rises in Mcl-1, which in turn makes cells more resistant to apoptosis. “We were very excited about that finding,” said Ekholm-Reed. The TSRI lab’s experiments quickly confirmed the chain of events in neurons: parkin keeps levels of Fbw7β under control, and Fbw7β keeps levels of Mcl-1 under control. Full silencing of Mcl-1 leaves neurons extremely sensitive to oxidative stress.
Members of the team suspect that this is the principal explanation for how parkin mutations lead to Parkinson’s disease. But perhaps more importantly, they believe that their discovery points to a broad new “neuroprotective” strategy: reducing the Fbw7β-mediated destruction of Mcl-1 in neurons, which should make neurons more resistant to oxidative and other stresses.
“If we can find a way to inhibit Fbw7β in a way that specifically raises Mcl-1 levels, we might be able to prevent the progressive neuronal loss that’s seen not only in Parkinson’s but also in other major neurological diseases, such as Huntington’s disease and ALS [amyotrophic lateral sclerosis],” said Reed.
Finding such an Mcl-1-boosting compound, he added, is now a major focus of his laboratory’s work.
(Source: scripps.edu)
Extroverts have more sensitive brain-reward system
Extroverts may be more outgoing and cheerful in part because of their brain chemistry, reports a study by Cornell neuroscientists.
People’s brains respond differently to rewards, say the neuroscientists. Some people’s brains release more of the neurotransmitter dopamine, which ultimately gives them more reasons to be excited and engaged with the world, says Richard Depue, professor of human development in the College of Human Ecology, who co-authored the study with graduate student Yu Fu.
Their study, published in Frontiers in Human Neuroscience in June, sheds new light on how differences in the way the brain responds to reward translate into extraverted behavior, the authors say.
“Rewards like food, sex and social interactions as well as more abstract goals such as money or getting a degree trigger the release of dopamine in the brain, producing positive emotions and feelings of desire that motivate us to work toward obtaining those goals. In extroverts, this dopamine response to rewards is more robust so they experience more frequent activation of strong positive emotions,” Depue says.
“Dopamine also facilitates memory for circumstances that are associated with the reward. Our findings suggest this plays a significant role in sustaining extroverted behavior,” Depue adds. “The extroverts in our study showed greater association of context with reward than introverts, which means that over time, extroverts will acquire a more extensive network of reward-context memories that activate their brain’s reward system.”
Over a week, the researchers engaged 70 young adult males – a mix of introverts and extroverts according to a standard personality test – in a set of laboratory tasks that included viewing brief video clips of several aspects of the lab environment. On the first four days, some participants received a low dose of the stimulant methylphenidate (MP), also known as Ritalin, which triggers the release of dopamine in the brain; the others received either a placebo or MP in a different lab location. The team tested how strongly participants associated contextual cues in the lab (presented in video clips) with reward (the dopamine rush induced by MP) by assessing changes in their working memory, motor speed at a finger-tapping task and positive emotions (all known to be influenced by dopamine).
Participants who had unconsciously associated contextual cues in the lab with the reward were expected to have greater dopamine release/reward system activation on day 4 compared with day 1 when shown the same video clips. This so-called “associative conditioning” response is exactly what the team found in the extroverts. The extroverts strongly associated the lab context with reward feelings, whereas the introverts showed little to no evidence of associative conditioning.
“At a broader level, the study begins to illuminate how individual differences in brain functioning interact with environmental influences to create behavioral variation. This knowledge may someday help us to understand how such interactions create more extreme forms of emotional behavior, such as personality disorders,” says Depue.
Ritalin Shows Promise in Treating Addiction
A single dose of a commonly-prescribed attention deficit hyperactivity disorder (ADHD) drug helps improve brain function in cocaine addiction, according to an imaging study conducted by researchers from the Icahn School of Medicine at Mount Sinai. Methylphenidate (brand name Ritalin®) modified connectivity in certain brain circuits that underlie self-control and craving among cocaine-addicted individuals. The research is published in the current issue of JAMA Psychiatry, a JAMA network publication.
Previous research has shown that oral methylphenidate improved brain function in cocaine users performing specific cognitive tasks such as ignoring emotionally distracting words and resolving a cognitive conflict. Similar to cocaine, methylphenidate increases dopamine (and norepinephrine) activity in the brain, but, administered orally, takes longer to reach peak effect, consistent with a lower potential for abuse. By extending dopamine’s action, the drug enhances signaling to improve several cognitive functions, including information processing and attention.
“Orally administered methylphenidate increases dopamine in the brain, similar to cocaine, but without the strong addictive properties,” said Rita Goldstein, PhD, Professor of Psychiatry at Mount Sinai, who led the research while at Brookhaven National Laboratory (BNL) in New York. “We wanted to determine whether such substitutive properties, which are helpful in other replacement therapies such as using nicotine gum instead of smoking cigarettes or methadone instead of heroin, would play a role in enhancing brain connectivity between regions of potential importance for intervention in cocaine addiction.”
Anna Konova, a doctoral candidate at Stony Brook University, who was first author on this manuscript, added, ”Using fMRI, we found that methylphenidate did indeed have a beneficial impact on the connectivity between several brain centers associated with addiction.”
Dr. Goldstein and her team recruited 18 cocaine addicted individuals, who were randomized to receive an oral dose of methylphenidate or placebo. The researchers used functional magnetic resonance imaging (fMRI) to measure the strength of connectivity in particular brain circuits known to play a role in addiction before and during peak drug effects. They also assessed each subject’s severity of addiction to see if this had any bearing on the results.
Methylphenidate decreased connectivity between areas of the brain that have been strongly implicated in the formation of habits, including compulsive drug seeking and craving. The scans also showed that methylphenidate strengthened connectivity between several brain regions involved in regulating emotions and exerting control over behaviors—connections previously reported to be disrupted in cocaine addiction.
“The benefits of methylphenidate were present after only one dose, indicating that this drug has significant potential as a treatment add-on for addiction to cocaine and possibly other stimulants,” said Dr. Goldstein. “This is a preliminary study, but the findings are exciting and warrant further exploration, particularly in conjunction with cognitive behavioral therapy or cognitive remediation.”
(Source: newswise.com)
Brain imaging shows how prolonged treatment of a behavioral disorder restores a normal response to rewards
Attention-deficit/hyperactivity disorder (ADHD) is characterized by abnormal behavioral traits such as inattention, impulsivity and hyperactivity. It is also associated with impaired processing of reward in the brain, meaning that patients need much greater rewards to become motivated. One of the common treatments for ADHD, methylphenidate (MPH), is known to improve reward processing in the short term, but the long-term effects have remained unclear.
Kei Mizuno from the RIKEN Center for Life Science Technologies, in collaboration with colleagues from several other Japanese research institutions, has now demonstrated that prolonged treatment with MPH brings about stable changes in brain activity that improve reward processing with a commensurate improvement in ADHD symptoms.
ADHD is thought to affect up to 5% of children worldwide, and about half of those will go on to experience symptoms of the disorder into adulthood. MPH treats the disorder by increasing the levels of the brain chemical dopamine, which is involved in reward processing.
To understand the effect of MPH on ADHD symptoms and specifically reward processing over the longer term, the researchers studied the reward response behavior of ADHD and healthy patients—all children or adolescents—before and after treatment with osmotic release oral system (OROS) MPH. They used functional magnetic resonance imaging (fMRI) to measure brain activity during a task that saw participants rewarded with payment, but in two different scenarios: a high and a low monetary reward condition.
“In the high monetary reward condition, participants earned higher than the expected reward; whereas in the low monetary condition, participants earned an average reward that was consistently lower than expected,” says Mizuno.
The brain images showed that before treatment with OROS-MPH, ADHD patients had lower than normal sensitivity to reward, as demonstrated by their abnormally low brain activity in two parts of the brain associated with reward processing—the nucleus accumbens and the thalamus—during testing under the low monetary reward scenario.
However, after three months of treatment with OROS-MPH, there was no difference in the activity of these brain areas in ADHD patients compared with the healthy controls under any of the reward conditions. Their sensitivity to reward had returned to normal, and the patients’ other ADHD symptoms also showed improvement.
Mizuno says that this study goes further than previous work. “We knew that acute MPH treatment improves reward processing in ADHD,” he explains. “Now we’ve revealed that decreased reward sensitivity and ADHD symptoms are improved by treatment for three months.”