the dual orexinhypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self-administrationalmorexant双重orexinhypocretin受体拮抗剂,在腹侧被盖区减弱乙醇自治.pdfVIP

The Dual Orexin/Hypocretin Receptor Antagonist, Almorexant, in the Ventral Tegmental Area Attenuates Ethanol Self-Administration 1 1 1 1,6 1 Subhashini Srinivasan , Jeffrey A. Simms , Carsten K. Nielsen , Steven P. Lieske , Jade J. Bito-Onon , 1 1 3,4,5 1,2 Henry Yi , Frederic Woodward Hopf , Antonello Bonci , Selena E. Bartlett * 1 Ernest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, California, United States of America, 2 Translational Research Institute, Queensland University of Technology, Brisbane, Queensland, Australia, 3 Intramural Research Program, National Institute of Drug Abuse, Baltimore, Maryland, United States of America, 4 Department of Neurology, University of California San Francisco, California, United States of America, 5 Solomon Snyder Department of Neuroscience, John Hopkins University, Baltimore, Maryland, United States of America, 6 Department of Mental Health, San Francisco Veteran Affairs Medical Center, San Francisco, California, United States of America Abstract Recent studies have implicated the hypocretin/orexinergic system in reward-seeking behavior. Almorexant, a dual orexin/ hypocretin R1 and R2 receptor antagonist, has proven effective in preclinical studies in promoting sleep in animal models and was in Phase III clinical trials for sleep disorders. The present study combines behavioral assays with in vitro biochemical and electrophysiological techniques to elucidate the role of almorexant in ethanol and sucrose intake. Using an operant self- ad