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Gulley, Joshua M. Gulley, Joshua M. Juraska, Janice M. Schantz, Susan L. Wickesberg, Robert E. Galvez, Roberto Sherrill, Luke K 2017-08-10T20:33:16Z 2017-08-10T20:33:16Z 2019-08-11T09:15:17Z 2017-04-21 2017-05 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. Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-05-01 The student, Luke Sherrill, accepted the attached license on 2017-04-20 at 15:13. The student, Luke Sherrill, submitted this Dissertation for approval on 2017-04-20 at 15:13. This Dissertation was approved for publication on 2017-04-21 at 09:16. DSpace SAF Submission Ingestion Package generated from Vireo submission #10941 on 2017-08-10 at 15:06:37 Made available in DSpace on 2017-08-10T20:33:16Z (GMT). No. of bitstreams: 3 SHERRILL-DISSERTATION-2017.pdf: 1484511 bytes, checksum: 08c8086a1458666eddf1f7d12822b287 (MD5) LICENSE.txt: 4210 bytes, checksum: 9abc3da9ab8fbff9ebe4e13d9685c76c (MD5) PROQUEST_LICENSE.txt: 4556 bytes, checksum: 749f80599e380e7c8b159a15687c30d1 (MD5) Previous issue date: 2017-04-21 Embargo set by: Colleen Fallaw for item 102809 Lift date: 2019-08-10T21:27:21Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system U of I Only Restriction Lifted for Item 102809 on 2019-08-11T09:15:17Z. application/pdf http://hdl.handle.net/2142/97756 en Copyright 2017 Luke Sherrill Amphetamine Adolescence Prefrontal cortex Working memory The effects of repeated amphetamine exposure during adolescence on behavior and prefrontal cortex function text text Psychology Psychology University of Illinois at Urbana-Champaign Dissertation Ph.D.