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.