Abstract

The expression of sexual behavior requires a proper balance between inhibition and excitation at cognitive, hormonal and neurochemical levels. Inhibition of sexual behavior is considered to be important and even crucial to maintain proper social cohesion and adaptation (i.e. in response to threat, aversion, culture, fertility). In humans, spreading of sexually transmitted diseases is often due to inappropriate and risky sexual behavior (e.g. multiple partners, no use of condoms) or to a loosening of inhibitions under the influence of drugs. It is therefore important to understand where these drugs (recreational, or prescription) act to induce disinhibited sexual behavior. In this thesis, the mechanisms of action of two drugs associated famously with sexual disinhibition but possessing two largely opposite mechanisms of action, alcohol and d-amphetamine, are investigated. This is done using a conditioned partner avoidance paradigm in which male rats are trained to avoid copulation with females bearing a conditioned inhibitory olfactory cue associated with non reward. This paradigm has been used previously to reveal the disinhibitory properties of low doses of alcohol. In the first chapter, it is established that d-amphetamine disrupts conditioned partner avoidance as d-amphetamine-treated males still copulate with females bearing the conditioned inhibitory cue. Furthermore, similar to alcohol, exposure to the inhibitory cue alone under the influence of d-amphetamine activates brain regions associated with sexual behavior and sexual reward. As alcohol is known to induce disinhibition of behavior in general and of sexual behavior in particular, the focus of the second and third chapters is to examine the potential neurotransmitters involved in the disinhibitory effect of alcohol. Using microdialysis, it is found that levels of dopamine in the nucleus accumbens are increased when alcohol-treated male rats are exposed to the sexually conditioned inhibitory cue. This increase is due to activation of dopaminergic neurons from the ventral tegmental area. On the other hand, neither alcohol nor the conditioned cue has an effect on glutamate or GABA levels in the nucleus accumbens. Together these data demonstrate that dopamine release in the nucleus accumbens via activation of dopaminergic neurons in the ventral tegmental area plays a permissive role in the disinhibitory effects of alcohol (and likely amphetamine) on the sexual behavior of male rats.