Hanbing Lu1, Svetlana Chefer1, Pradeep Kurup1, Karine Guillem2, D. Bruce Vaupel1, Thomas J. Ross1, Yihong Yang1, Laura L. Peoples2, Elliot A. Stein1
1Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD, United States; 2Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA
Drug abuse remains a serious social problem. Long-lasting neuroadaptations following repeated drug exposure are thought to mediate compulsive drug seeking and taking behavior. In the present study, rats were trained to self-administered (SA) either I.V. cocaine (n=10) or oral sucrose (n=13) for 20 days using a long-access exposure regimen (6-h sessions), followed by 30 days of abstinence. A third untreated group (nave rats, n=10) served as a control. Following an acute cocaine challenge, rats with repeated cocaine exposure history demonstrate significantly reduced response. In particular, in such regions as the prelimbic cortex, the infralimbic cortex and the ACC, cocaine SA rats have negative fMRI response, in contrast to positive response in cocaine nave rats. These findings reinforce the role of prefrontal cortex in translation of motivational stimuli into adaptive motor response.