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January 19, 2007

Dopaminergic Neurochemical Alterations due to Sub-chronic Nicotine Exposure in Adolescent vs. Adult

Frances Leslie, Ph.D, Susan McQuown

James Horne, Department of Pharmacology at University of California, Irvine, Summer 2006

Adolescence is a critical period for onset of illicit drug use, usually initiating with tobacco and slowly progressing to harder drugs. These findings suggest that adolescence is a critical period in which nicotine may be a ‘gateway’ to illicit drug use. We previously illustrated that adolescent rats pretreated with a subchronic low-dose of nicotine quickly acquired cocaine self-administration compared to rats treated with saline. Moreover, adult rats with the same pretreatment did not demonstrate the same behavioral patterns demonstrating that nicotine effect is age-specific. In this study, we investigate the neural alterations caused by nicotine during adolescence. Rats were given intravenous injections of nicotine or saline spaced 1 minute apart, daily for 4 days. Rats were euthanized and their brains were harvested for quantitative autoradiography studies. Autoradiography will be used to measure the density of dopaminergic receptors and transporters, as well as serotonin transporters. MCID analysis will be used to analyze changes in binding densities in particular brain regions. We propose that nicotine-induced neural alterations in the dopaminergic system are the underlying mechanism of increased cocaine self-administration in adolescent rats.