Scientists have identified a brain mechanism in rats that may play acentral role in regulating anxiety and alcohol-drinking. The finding,by researchers supported by the National Institute on Alcohol Abuse andAlcoholism (NIAAA), part of the National Institutes of Health (NIH),could provide important clues about the neurobiology ofalcohol-drinking behaviors in humans. A report of the study appears inthe October 3, 2005 issue of the Journal of Clinical Investigation.
"This is an intriguing finding," notes NIAAA Director Ting-Kai Li,M.D. "These experiments, conducted in rats selectively bred to have ahigh affinity for alcohol, help us address questions about thepotential role that anxiety might play in human alcoholism. Thesemolecular studies also may reveal potential targets for therapy ofanxiety and alcoholism."
Some researchers have suggested that high levels of anxiety may predispose some individuals to becoming alcoholic.
Researchers led by Subhash C. Pandey, Ph.D., Associate Professorand director of neuroscience alcoholism research in the Department ofPsychiatry at the University of Illinois and Jesse Brown VA MedicalCenter in Chicago, found that "P" rats, a strain bred to preferalcohol, showed more anxiety-like behaviors and drank more alcohol,than non alcohol-preferring "NP" rats. They measured anxiety in therats with an apparatus known as an elevated plus-maze, which consistsof two open arms and two closed arms connected to a central platform.Anxiety is gauged as a function of the amount of time a rat spends inthe closed versus the open arms of the maze during a 5-minute testingperiod -- the greater an animal's level of anxiety, the less open-armactivity it displays.
Dr. Pandey and his colleagues also found that levels of CREB, aprotein involved in a variety of brain functions, were lower in certainbrain areas of P rats compared with NP rats. Levels of neuropeptide Y(NPY), a molecule that regulates the function of severalneurotransmitters and is known to play a role in anxiety andalcohol-drinking behaviors, also were lower in P rats. One function ofCREB is to regulate the production of NPY.
"Compared to NP rats, levels of CREB and NPY were innatelylower in the central amygdala and medial amygdala of P rats," explainsDr. Pandey, "brain areas which play a crucial role in anxiety behaviorsand which have been shown previously to be involved in rewarding,reinforcing, and motivational aspects of alcohol drinking behaviors.And turning off CREB function in the central amygdala of NP rats makesthem look like P rats -- more anxious and thus more likely to drink."
Alcohol intake reduced anxiety-like behaviors in the P rats, aneffect that was associated with increased CREB function and NPYproduction in the central and medial amygdala. And by administeringcompounds that promote CREB function and NPY production in the centralamygdala, researchers were able to reduce anxiety -- and alcohol intake-- in P rats. On the other hand, by disrupting CREB function (and theconcomitant NPY production) in the central amygdala of NP rats, theresearchers were able to provoke anxiety-like behavior and promotealcohol intake in those animals.
Dr. Pandey and his colleagues proposed that decreasedCREB-dependent NPY production in the central amygdala might be apre-existing condition for anxiety and alcohol-drinking behaviors.
"Our findings implicate this pathway in genetic predispositionto high anxiety and alcohol-drinking behaviors of P rats," says Dr.Pandey. "Future studies should explore the relationship of otherCREB-related compounds to these phenomena in P rats or other animalmodels."
The National Institute on Alcohol Abuse and Alcoholism, a componentof the National Institutes of Health, U.S. Department of Health andHuman Services, conducts and supports approximately 90 percent of theU.S. research on the causes, consequences, prevention, and treatment ofalcohol abuse, alcoholism, and alcohol problems and disseminatesresearch findings to general, professional, and academic audiences.Additional alcohol research information and publications are availableat www.niaaa.nih.gov.
Materials provided by NIH/National Institute on Alcohol Abuse and Alcoholism. Note: Content may be edited for style and length.
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