Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Anatomy and Cell Biology

Supervisor

Dr. Lique M. Coolen

Abstract

Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus (HIV). Currently, the neurobiological basis for this drug-sex nexus is unknown. Moreover, there is a lack of studies investigating the effects of Meth on sexual behavior and more importantly, compulsive sex-seeking behavior, under controlled experimental settings in animal models. First, using immuhistochemistry for mating- and Meth-induced neural activation it was demonstrated that Meth administration in male rats activates neurons in brain regions of the limbic system that are involved in the regulation of sexual behavior. Specifically, Meth and mating co-activated neurons in the nucleus accumbens (NAc) core and shell, basolateral amygdala (BLA), anterior cingulate (ACA) and orbitofrontal (OFC) cortices. Second, the effects of acute or chronic administration of Meth on different aspects of sexual behavior were tested including motivation and performance, compulsive behavior, and reward. Results showed that high doses of Meth inhibited sexual motivation and performance. Next, to investigate Meth effects on compulsive sexual behavior a paradigm was established in which visceral illness induced by lithium chloride (LiCl) was paired with sexual reward. A low Meth dose (1mg/kg; s.c.) that does not impair sexual function had long-term effects on compulsive sexual behavior. Specifically, two weeks following the last Meth administration, Meth-pretreated males displayed sex-seeking behavior despite having learned the adverse consequences of mating. This effect was dependent on Meth administration being concurrent with sexual experience. Finally, using a conditioned place preference (CPP) paradigm, it was shown that concurrent Meth and sex experience was required for enhanced CPP for mating with Meth and for Meth alone. In contrast, reward for mating alone was decreased. Together, these findings illustrate that Meth can activate the same neurons as sexual behavior and in turn may alter this natural reward behavior. Moreover, these data indicate that the association between drug use and mating may be required for expression of compulsive sex behavior reported by Meth users and is correlated with increased reward seeking for concurrent Meth exposure and mating.

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