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Research by UNC Scientist Reveals Alcohol-Specific Neural Substrate in the Brain's

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Research by UNC Scientist Reveals Alcohol-Specific Neural Substrate in the Brain's UNC Researcher Receives K01 Award to Develop New Research Directions Sandeep Kumar, M.D., assistant profes- training in confocal microscopy to inves- sor of psychiatry and member of the Bowles tigate receptor trafficking or movement be- Center for Alcohol Studies, recently received tween the cell membrane and intracellular Center Line the Mentored Research Scientist Develop- compartments and the use of transgenic Bowles Center for Alcohol Studies ment Award (K01) from the National In- mouse technology. His research efforts also School of Medicine, University of North Carolina at Chapel Hill stitutes of Health (NIH) to develop an in- include collaborations with senior scien- Our mission is to conduct, coordinate, and promote basic and clinical research on the causes, prevention, and treatment of alcoholism and alcoholic disease. dependent research program that extends his tists to develop new methods for investi- ISSN 0738-6567 post-doctoral research in new directions. Dr. gating the phosphorylation of GABAA re- Volume 16, Number 4, December 2005 Kumar is collaborating with mentor A. ceptors in brain tissue. His new studies will Leslie Morrow, Ph.D. to elucidate the mo- provide important mechanistic informa- lecular mechanisms that underlie alterations tion on the molecular basis of ethanol-in- Research by UNC Scientist Reveals Alcohol-Specific γ in -aminobutyric acid type A (GABAA) re- duced adaptations in GABAA receptors ceptor adaptations that influence the devel- that influence the development of ethanol Neural Substrate in the Brain’s “Reward Circuit” opment of ethanol dependence. He is fo- tolerance and dependence. Sandeep Kumar, M.D. Cocaine, alcohol, food, gambling, sex, collaborator Dr. Regina Carelli of UNC’s necessary for sustaining life. cusing on the role of receptor trafficking in Dr. Kumar completed undergraduate plastic surgery: the list of substances and Psychology Department, Robinson is in- Robinson studies neural correlates of al- mediating GABA receptor adaptations. and medical studies at the Ranchi Univer- A activities to which addictions are said to vestigating a brain area known as the cohol-motivated behavior in the nucleus The award will provide Dr. Kumar with sity, India. He completed a residency in Ra- be established is long and growing. Nei- nucleus accumbens. Often characterized as accumbens of rats in a paradigm similar to diology at the Rajendra Medical College, India, and came ther lay people nor scientists dispute the a main component of the brain’s “reward that previously employed by collaborator to the United States to undertake research fellowships at The Bowles Center for existence of addictions to psychoactive sub- system,” the nucleus accumbens receives Carelli to study neural correlates of cocaine- Wake Forest University and the University of North Caro- stances such as cocaine or alcohol. How- converging neural input from brain areas motivated behavior. Carelli measured the Alcohol Studies lina at Chapel Hill. Dr. Kumar first worked in alcohol re- ever, whether addictions also develop to involving memory, emotion, and informa- electrical activity of single nerve cells (neu- Tel. (919) 966-5678 search as a post-doc with Dr. A. Leslie Morrow, associate Fax. (919) 966-5679 basic physiologic require- rons) in the nucleus director of the Bowles Center and professor of Psychiatry ments such as food and sex accumbens in rats trained to To become involved in our mission, call and Pharmacology. He trained in biochemical techniques Melissa Mann at (919) 966-5678 or email and to higher-order behav- press a lever to receive an in- including chloride flux assays and protein expression meth- [email protected]. iors such as gambling is travenous infusion of cocaine. ods. Successful in his previous endeavors, he wants to ex- For treatment information call UNC Health controversial. Addiction in- She found that specific sub- pand his training and horizons to address new questions Care’s Alcohol and Substance Abuse Program volves the compulsive need sets of neurons in the nucleus at (919) 966-6039 or (888) 457-7457. and begin his own research program. When speaking of for and use of a substance, accumbens appear to encode his experience at UNC, Dr. Kumar said, “I have benefited and establishment of an ad- for different aspects of goal- immensely from the mentoring of Dr. Leslie Morrow and diction (at least in its early directed responding for co- the intellectual environment of the Bowles Center. My ex- stages) entails behavior caine. Some neurons exhib- posure to alcohol research greatly influenced my decision motivated by the goal of ited changed (either increased to pursue a career in research rather than clinical prac- achieving reward or rein- or decreased) electrical activ- www.med.unc.edu/alcohol tice.” forcement. Are all rewards ity immediately before the rat created equal, and is it ac- pressed the lever whereas oth- Center Line, Vol. 16 No. 4 Published quarterly to bring greater understanding of alcoholism research and the Center’s mission. Robinson and Carelli Alcohol Research Group: Wilbur Williams, Regina A. Leslie Morrow, Ph.D., Editor-in-Chief; Angela D. Farrior, Managing Editor; Jane Saiers, Ph.D., Science Writer curate to label the gamut of ers exhibited such changes compulsive, excessive be- Carelli, Ph.D., Donita Robinson, Ph.D., Amber Kinard, and Scott McConnell within seconds after the lever haviors directed at these re- press. No such changes were UNC Bowles Center for Alcohol Studies Non-Profit Organization wards as addictions? Is the cocaine addict tion processing—functions integral to goal- observed in rats pressing a lever that was CB# 7178, Thurston-Bowles Building US Postage motivated by the same drives as the com- directed behavior. Neuroscientists consider not associated with cocaine reward. University of North Carolina at Chapel Hill PAID the nucleus accumbens an important neu- To test the hypothesis that the same Chapel Hill, North Carolina 27599-7178 Permit No. 177 pulsive gambler? Is the overeater who at- Chapel Hill, NC 27599-1800 tempts to diet but feels helpless to control ral substrate for motivated behavior involv- neural circuitry that mediates goal-directed his eating confronted by the same physical ing “natural” rewards such as water, food, behavior involving “natural” rewards also and psychological challenges as the alco- and sex. According to a major hypothesis mediates goal-directed behavior involving holic who tries to but cannot abstain from in drug abuse research, the nucleus drugs of abuse, Carelli went on to examine drinking? accumbens is also an important neural sub- whether the same neurons are activated Dr. Donita Robinson, Assistant Profes- strate for motivated behavior involving when animals engage in goal-directed be- sor in the University of North Carolina’s drugs of abuse. It is postulated that addic- havior for cocaine and natural (water) re- Psychiatry Department and the Bowles tions can be so difficult to overcome be- ward. She found that specific neurons in Center for Alcohol Studies, is approach- cause they tap into the same brain circuits the nucleus accumbens encoded for re- ing answers to some of these questions by that evolved to ensure that the organism sponding for water and food; however, only studying the neural underpinnings of re- seeks and obtains those rewarding sub- 8% of those same neurons were activated ward-seeking behavior in animals. With stances, such as food and water, that are during goal-directed behavior involving This document is supported by subscriptions and donations to the Bowles Center for Alcohol Studies. Continued on next page cocaine. The overlap was much greater dur- water (Figure). Robinson presented these re- Post-Doctoral ing responding for two “natural” rewards: ap- sults at this year’s Society for Neuroscience proximately 70% of neurons studied had simi- meeting in Washington, DC. The Director’s Column Fellowships lar responses to the “natural” rewards of wa- Robinson’s and Carelli’s research provides Now Available! ter and food. These results suggest that, while new insights into the neural basis of goal-di- Fulton T. Crews, Ph.D. the nucleus accumbens is a neural substrate rected behavior. Consistent with current un- Director, Bowles Center for The Bowles Center for Alcohol Studies is offering post- for behavior involving both “natural” rewards derstanding, their research shows the nucleus Alcohol Studies doctoral fellowships in a multidisciplinary training pro- and cocaine, different microcircuits in the accumbens, an integral part of the brain’s re- gram funded by NIAAA. Research is focused on mo- nucleus accumbens encode for natural-re- ward circuit, to be important in processing lecular and cellular studies on alcohol actions. ward-mediated behavior versus cocaine-me- information about motivated responding in- diated behavior. volving “natural” rewards as well as drugs of Applicants must have an M.D. or Ph.D., U.S. citizen- Robinson has modified and extended this abuse. Their research augments current un- ship or permanent residency, and an interest in alco- hol research. Send applications to a faculty mentor Donita Robinson, PhD paradigm to study the effects of goal-directed derstanding by showing that the neural sub- This issue of the Centerline highlights two new junior faculty who of interest. behavior for alcohol on neural activity in the strate for reward-motivated behavior is not are carrying the cutting edge of alcohol research forward. Alcohol is nucleus accumbens. Like cocaine,
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