Neuroscience

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Major dopamine system helps restore consciousness after general anesthesia
Researchers may be one step closer to better understanding how anesthesia works. A study in the August issue of Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®), found stimulating a major dopamine-producing region in the brain, the ventral tegmental area (VTA), caused rats to wake from general anesthesia, suggesting that this region plays a key role in restoring consciousness after general anesthesia. Activating this region at the end of surgery could provide a novel approach to proactively induce consciousness from anesthesia in surgical patients, researchers say.
"While generally safe, it is well known that patients should not be under general anesthesia longer than necessary," said Ken Solt, M.D., lead author, Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine and assistant professor of anesthesia, Harvard Medical School, Boston. "Currently, there are no treatments to reverse the effects of general anesthesia. We must wait for the anesthetics to wear off. Having the ability to control the process of arousal from general anesthesia would be advantageous as it might speed recovery to normal cognition after surgery and enhance operating room (O.R.) efficiencies."
Although the brain circuits that drive the process of emerging from general anesthesia are not well understood, recent studies suggest that certain arousal pathways in the brain may be activated by certain drugs to promote consciousness. The authors previously reported that methylphenidate (Ritalin), a drug used to treat attention deficit hyperactivity disorder, awakened rats from general anesthesia by activating dopamine-releasing pathways.
In the current study, rats were given the general anesthetics isoflurane or propofol. Once unconscious, researchers performed targeted electrical stimulation, through implanted steel electrodes, on the two major regions of the rats’ brains that contain dopamine-releasing cells – the VTA (the area of the brain that controls cognition, motivation and reward in humans) and the substantia nigra, which controls movement.
Researchers found that electrical stimulation of the VTA caused the rats to regain consciousness, suggesting that dopamine released from cells in this area of the brain is likely involved in arousal. Interestingly, electrical stimulation of the VTA had an effect similar to that of the drug methylphenidate in restoring consciousness after anesthesia.
"We now have evidence that dopamine released by cells in the VTA is mainly responsible for the awakening effect seen with methylphenidate," said Dr. Solt. "Because dopamine-releasing cells in the VTA are important for cognition, we may be able to use drugs that act on this region not only to induce consciousness in anesthetized patients, but to potentially treat common postoperative emergence-related problems such as delirium and restore cognitive function."

Major dopamine system helps restore consciousness after general anesthesia

Researchers may be one step closer to better understanding how anesthesia works. A study in the August issue of Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®), found stimulating a major dopamine-producing region in the brain, the ventral tegmental area (VTA), caused rats to wake from general anesthesia, suggesting that this region plays a key role in restoring consciousness after general anesthesia. Activating this region at the end of surgery could provide a novel approach to proactively induce consciousness from anesthesia in surgical patients, researchers say.

"While generally safe, it is well known that patients should not be under general anesthesia longer than necessary," said Ken Solt, M.D., lead author, Massachusetts General Hospital Department of Anesthesia, Critical Care and Pain Medicine and assistant professor of anesthesia, Harvard Medical School, Boston. "Currently, there are no treatments to reverse the effects of general anesthesia. We must wait for the anesthetics to wear off. Having the ability to control the process of arousal from general anesthesia would be advantageous as it might speed recovery to normal cognition after surgery and enhance operating room (O.R.) efficiencies."

Although the brain circuits that drive the process of emerging from general anesthesia are not well understood, recent studies suggest that certain arousal pathways in the brain may be activated by certain drugs to promote consciousness. The authors previously reported that methylphenidate (Ritalin), a drug used to treat attention deficit hyperactivity disorder, awakened rats from general anesthesia by activating dopamine-releasing pathways.

In the current study, rats were given the general anesthetics isoflurane or propofol. Once unconscious, researchers performed targeted electrical stimulation, through implanted steel electrodes, on the two major regions of the rats’ brains that contain dopamine-releasing cells – the VTA (the area of the brain that controls cognition, motivation and reward in humans) and the substantia nigra, which controls movement.

Researchers found that electrical stimulation of the VTA caused the rats to regain consciousness, suggesting that dopamine released from cells in this area of the brain is likely involved in arousal. Interestingly, electrical stimulation of the VTA had an effect similar to that of the drug methylphenidate in restoring consciousness after anesthesia.

"We now have evidence that dopamine released by cells in the VTA is mainly responsible for the awakening effect seen with methylphenidate," said Dr. Solt. "Because dopamine-releasing cells in the VTA are important for cognition, we may be able to use drugs that act on this region not only to induce consciousness in anesthetized patients, but to potentially treat common postoperative emergence-related problems such as delirium and restore cognitive function."

Filed under anesthesia consciousness ventral tegmental area dopamine ritalin neuroscience science

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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)

Filed under ritalin addiction ADHD dopamine methylphenidate cocaine addiction neuroscience science

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Research Shows How Ritalin Affects Brains of Kids With ADHD

Ritalin activates specific areas of the brain in children with attention-deficit/hyperactivity disorder (ADHD), mimicking the brain activity of children without the condition, a new review says.

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"This suggests that Ritalin does bring the brain [of a child with ADHD] back to the brain the typically developing kid has," said study author Constance Moore, associate director of the translational center for comparative neuroimaging at the University of Massachusetts Medical School.

Analyzing data from earlier studies that looked at how children’s brains were affected by doing certain tasks that are sometimes challenging for kids with ADHD, the researchers found that Ritalin (methylphenidate) was having a visible impact on three areas of the brain known to be associated with ADHD: the cortex, the cerebellum and the basal ganglia.

The study could be helpful in diagnosing and treating children with ADHD, Moore said. “It may be helpful to know that in certain children, Ritalin is having a physiological effect in the areas of the brain involved with attention and impulse control,” she said.

The research was published recently in the Harvard Review of Psychiatry.

Nine studies analyzed by the researchers used functional MRI to evaluate brain changes after children had taken a single dose of Ritalin. The children were involved in different types of tasks that tested their ability to focus and inhibit an impulse to act.

For example, to observe the brain’s reaction during a test of what is called “inhibitory control,” a child was told that every time he saw a zero show up on a screen, he should push the button on the right; every time he saw an X appear, he should push the left button. The children would then be asked to flip their responses, pushing the left button when they saw a zero.

"That’s hard to do," Moore said, "because you’ve developed the habit [of pushing the other button], so you have to suppress your impulse. If you do 20 zeros and keep pressing and then you see an X, most kids with ADHD will hit the wrong button."

In three out of five of the inhibitory control studies, Ritalin at least partially normalized brain activation in ADHD children.

To note how the brain reacted to a selective attention test, Moore said, children would first be asked, for example, what word they were seeing. The word would be “red,” and the color of the type also would be red. Then they would be shown the word “red,” but the color of the type would be green. In several studies, Ritalin affected activation in the frontal lobes during such inhibitory control tasks.

Most of the studies included in the review were performed in the United States or the United Kingdom. The majority of participants were adolescent boys, and all studies compared their results to healthy children of the same approximate age.

Because none of the studies looked at the correlation between ADHD symptoms and whether the child was taking Ritalin, there is no way to link the changes in brain activation with clinical improvement, Moore said. “It’s possible that kids who are not responsive to Ritalin may have brain changes too,” she said.

ADHD affects between 3 percent and 7 percent of school-aged children in the United States, according to the American Psychiatric Association. Boys are more likely to have ADHD than girls.

One expert was not surprised by the results.

"The review article shows there is a consensus of well-designed imaging studies showing that [Ritalin] has an impact on the frontal cortex of the brain, where we have long believed these patients have issues," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at the Steven & Alexandra Cohen Children’s Medical Center of New York, in New Hyde Park. Adesman wondered if Ritalin may play a role in helping the brain mature.

"Their data provides partial support for that," he said. "But if anything, the medicine seems to help the brain look more normal and doesn’t seem to do anything bad to it."

(Source: consumer.healthday.com)

Filed under ADHD ritalin brain activity neuroimaging methylphenidate cortex neuroscience science

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ADHD medicine affects the brain’s reward system
A group of scientists from the University of Copenhagen has created a model that shows how some types of ADHD medicine influence the brain’s reward system. The model makes it possible to understand the effect of the medicine and perhaps in the longer term to improve the development of medicine and dose determination. The new research results have been published in the Journal of Neurophysiology.
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ADHD medicine affects the brain’s reward system

A group of scientists from the University of Copenhagen has created a model that shows how some types of ADHD medicine influence the brain’s reward system. The model makes it possible to understand the effect of the medicine and perhaps in the longer term to improve the development of medicine and dose determination. The new research results have been published in the Journal of Neurophysiology.

Read more

Filed under ADHD ADHD medicine Ritalin reward-punishment dopamine neuroscience science

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Long-term ADHD drug use appears safe, brain development not affected

July 18, 2012

Drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) do not appear to have long-term effects on the brain, according to new animal research from Wake Forest Baptist Medical Center.

As many as five to seven percent of elementary school children are diagnosed with ADHD, a behavioral disorder that causes problems with inattentiveness, over-activity, impulsivity, or a combination of these traits. Many of these children are treated with psychostimulant drugs, and while doctors and scientists know a lot about how these drugs work and their effectiveness, little is known about their long-term effects.

Linda Porrino, Ph.D., professor and chair of the Department of Physiology and Pharmacology, along with fellow professor Michael A. Nader, Ph.D., both of Wake Forest Baptist, and colleagues conducted an animal study to determine what the long-lasting effects may be. Their findings were surprising, said Porrino. “We know that the drugs used to treat ADHD are very effective, but there have always been concerns about the long-lasting effects of these drugs,” Porrino said.

"We didn’t know whether taking these drugs over a long period could harm brain development in some way or possibly lead to abuse of drugs later in adolescence."

Findings from the Wake Forest Baptist research are published online this month in the journal Neuropsychopharmacology.

The researchers studied 16 juvenile non-human primates, whose ages were equivalent to 6-to 10-year-old humans. Eight animals were in the control group that did not receive any drug treatment and the other eight were treated with a therapeutic-level dose of an extended-release form of Ritalin, or methylphenidate (MPH), for over a year, which is equivalent to about four years in children. Imaging of the animals’ brains, both before and after the study, was conducted on both groups to measure brain chemistry and structure. The researchers also looked at developmental milestones to address concerns that ADHD drugs adversely affect physical growth.

Once the MPH treatment and imaging studies were concluded, the animals were given the opportunity to self administer cocaine over several months. Nader measured their propensity to acquire the drug and looked at how rapidly and in what amounts, to provide an index of vulnerability to substance abuse in adolescence. As reported in the research paper, they found no differences between groups – monkeys treated with Ritalin during adolescence were not more vulnerable to later drug use than the control animals.

"After one year of drug therapy, we found no long-lasting effects on the neurochemistry of the brain, no changes in the structure of the developing brain. There was also no increase in the susceptibility for drug abuse later in adolescence," Porrino said. "We were very careful to give the drugs in the same doses that would be given to children. That’s one of the great advantages of our study is that it’s directly translatable to children."

Porrino said non-human primates provide exceptional models for developmental research because they undergo relatively long childhood and adolescent periods marked by hormonal and physiological maturation much like humans.

"Our study showed that long-term therapeutic use of drugs to treat ADHD does not cause long-term negative effects on the developing brain, and importantly, it doesn’t put children at risk for substance abuse later in adolescence," she said.

One of the exciting things about this research, Porrino said, is that a “sister” study was conducted simultaneously at John Hopkins with slightly older aged animals and different drugs and their findings were similar. “We feel very confident of the results because we have replicated each other’s studies within the same time frame and gotten similar results,” she said. “We think that’s pretty powerful and reassuring.”

Provided by Wake Forest University Baptist Medical Center

Source: medicalxpress.com

Filed under science neuroscience brain psychology drug ADHD disorder pharmacology long-term treatment ritalin

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