Cognitive impairment and altered drug sensitivity are two commonly reported behavioral outcomes of amphetamine abuse. Individuals who begin using amphetamine during adolescence may have an increased risk of developing drug-related problems because of maturational changes in mesocorticolimbic circuitry that are specific to this stage of development. The studies presented here were designed to assess long-term effects of amphetamine on cognition, dopamine receptor function, and prefrontal cortex (PFC) activity, with a focus on the consequences of drug exposure during adolescence. Chapter 1 includes a review of the literature on substance abuse and PFC dysfunction along with the specific aims of the studies described in the following chapters. Chapter 2 describes studies of drug-induced psychomotor activity and measures of working memory in rats exposed to amphetamine during adolescence or adulthood. Results suggest long-term effects of amphetamine on cognition vary according to the age of exposure. The experiments in Chapter 3 investigated the protracted effects of repeated amphetamine exposure during adolescence on psychomotor behavior and medial PFC function in young adulthood. Relative to controls, rats pre-exposed to amphetamine displayed psychomotor sensitization when challenged with amphetamine and heightened responsiveness to D1 and D2 receptor agonists. Expression of sensitization to amphetamine was attenuated in pre-exposed rats following challenges with a D1 or D2 receptor antagonist. The long-term functional impact of amphetamine on medial PFC neurons was assessed using single-unit recordings in awake behaving rats. Young adult rats were challenged with amphetamine followed by a D1 or D2 receptor antagonist. The proportion of amphetamine-responsive neurons and the pattern of spike activity was altered in animals exposed to amphetamine during adolescence relative to controls. Finally, Chapter 4 includes a general discussion on the results and implications of the experiments described in this dissertation. Taken together, the research presented here demonstrates age-dependent effects of amphetamine on cognition and highlights the long-lasting impact of amphetamine exposure on dopamine and medial PFC function
