Date of Award

Spring 2021

Document Type

Open Access Dissertation



First Advisor

Steven Harrod


The neurobiological processes which determine the choice between 2 (or more) reinforcers are unidentified despite the remarkable benefits which could result from better understanding or control of such processes. Most prominently, reducing choices to pursue drug over non-drug reinforcers could curtail the development or continuation of drug dependence. Likewise, increasing goal-directed behavior in single-schedule and choice settings may alleviate some of the consequences of apathy, a reduction in goal-directed behavior which can occur with neuropathologies including HIV-associated neurocognitive disorders. Dysregulation of the mesolimbic circuit, connecting the ventral tegmental area to the nucleus accumbens, has been implicated in both drug dependence and in apathy and is thus a propitious target for the manipulation of reinforcer intake. After training animals to lever-press for sucrose and cocaine under single-schedule and choice (cocaine vs. sucrose) procedures, the current experiment utilized DREADDs (designer receptors exclusively activated by designer drugs) retroviral technique to bidirectionally manipulate the activity of designer human M3 muscarinic and kappa opioid receptors within the mesolimbic circuit. As hypothesized, biological sex influenced genotype-differences and choice behavior supporting that F344/N females and HIV-1 Tg females, respectively, may be more vulnerable to drug dependence and apathy than males within their given genotype. Significantly, mesolimbic stimulation reduced choice for cocaine over sucrose in F344/N females and males. Mesolimbic stimulation did not have a clear influence on HIV-1 Tg animals’ reinforcer intake in the choice procedure despite influencing sucrose intake in the single-schedule procedure. Besides informing hypotheses regarding the unknown neurobiological mechanisms which determine choice behaviors, the current choice procedure revealed biological sex and presence of the HIV-1 transgene as factors which influence the effect of mesolimbic stimulation on choice behavior, establishing the procedure as a valuable tool for identifying factors which may exacerbate resistance to treatments

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