Grant: Discovery Grants Program - Individual

The main objective of the proposed research is to continue our identification of specific neuroanatomical and neurochemical systems that excite or inhibit appetitive and consummatory aspects of sexual behavior in male and female rats. We have concentrated our efforts in the previous grant cycle around understanding the excitatory role of the medial preoptic area (mPOA) of the anterior hypothalamus and its interaction with regions of the ventromedial hypothalamus, ventral tegmental area (VTA), and medial amygdala. The proposed research will extend this work to investigate the role played by dopamine, oxytocin, vasopression, melanocortins, and opioids, in controlling appetitive sexual behaviors, and how those neurochemical systems are activated by unconditioned and conditioned olfactory, somatosensory, and genital stimuli. Recently, we have turned our attention to the role of cortical structures in sexual inhibition, notably the medial prefrontal, cingulate, and insular cortices, and their outputs to the mPOA, VTA, and nucleus accumbens (NAc). We propose to examine the role played by serotonin in these regions in the ""top-down"" control of sexual inhibition using paradigms established in our lab of sexual refractoriness in male rats, estrus termination in female rats, conditioned inhibition, and alcohol-induced disinhibition. We are also interested in the role played by first experiences with sexual reward and how they alter, via epigenetic mechanisms, the activation of excitatory systems. The proposed research will utilize a combination of neuropharmacological techniques, including in vivo neurochemical analyses using receptor-selective antagonists, autoradiography, molecular biological techniques for staining activated neurons in tissue, and epigenetic techniques to inactivate demethylation enzymes, to examine the role of different brain regions and neurochemical systems. A second related line of research seeks to understand the role played by clitoral stimulation (CLS) in female rat sexual reward and appetitive sexual motivation. We have found that CLS induces conditioned place preference, and activates regions of the mPOA, VTA, NAc, and amygdala. We have also recently discovered that such stimulation also induces an orgasm-like response in females, accompanied by specific vocalization patterns that resemble those in male rats during penile stimulation and after ejaculation (although the female pattern is higher in the kHz range and more complex). We propose to examine how these responses depend on steroid hormone priming, and are altered by sexual nonreward induced by opioid antantagonism, conditioned association with sexually nonreceptive partners, or by SSRIs that inhibit orgasm. These studies will take our research to the next level by examining the activation of neurochemical and molecular systems associated with sexual excitation and inhibition.