Grant: Operating Grant

Sexual dysfunctions affect a substantial number of people worldwide, with North American estimates ranging from 10-60% of men and women, depending on the particular type of dysfunction. Unlike sexual arousal disorders such as erectile dysfunction or lack of vaginal blood flow, sexual desire and orgasm disorders are more complex and involve experience and expectation, processes that are controlled by the brain. At present, very little is understood about the neural mechanisms involved, although a growing body of evidence from animal models has identified excitatory and inhibitory systems in the brain that likely play a role. Our previous CIHR-funded studies revealed a strong link in both male and female rats between the experience and expectation of sexual reward and behaviors aimed at sexual contact. Such behaviors are analogous to human sexual desire. Sexual reward states are critically dependent on the activation of endogenous opioid systems. We will utilize these models of sexual reward in the present proposal to study the ability of odor and tactile cues to be associated with sexual excitation or inhibition, and then to use the cues as "priming stimuli" to examine whether they activate or inhibit neurotransmitter systems in the brain associated with exitation (e.g., dopamine, oxytocin) or reward (opioids like endorphin). We will also examine how experience with sexual nonreward comes to induce conditioned sexual inhibition, and how the cues stimulate a pattern of brain activation that is different from the patter induced by the same cue associated with sexual excitation. Finally, we will examine how excitatory and inhibitory cues interact, and whether a cue that primes excitation in the brain can override the reaction to an inhibitory cue. These studies will have important implications for our understanding of the etiology and maintenance of sexual dysfunction, and for the design of drug therapies to treat sexual desire and orgasm disorders.