This proposal requests continued support for a comparative, multidisciplinary research program that seeks to understand (i) the evolution of hormone-brain-behavior mechanisms underlying sexual behaviors, and (ii) the dual neural circuits that subserve these behaviors. The comparative method emphasizes the need for different model systems so as to elucidate the general rules which govern behaviors, as well as their historical roots. Multidisciplinary studies spanning molecular to population levels of biological organization provide a multifaceted, yet integrated, perspective of individual behavior. The animal models include parthenogenetic or all-female whiptail lizards and their sexual ancestors as well as transgenic mice. The unisexual species is known to have descended directly from the sexual species, thereby allowing ancestor-descendent comparisons. Further, because all parthenogenetic individuals have ovaries, yet exhibit both male-like and female-like pseudosexual behaviors, the complication of having two gonadal sexes, each with their own particular hormonal milieu, is removed. This makes it possible to study the neural circuits that underlie mounting and receptive behavior in a manner not possible with more common laboratory animals. The discovery that males can be created in this otherwise all-female species provides a unique opportunity to investigate the respective roles of genetics and gonadal hormones in the determination of adult sexual behavior and the underlying neural phenotype. Finally, the research based on the discovery that progesterone is an important modulator of male sexual behavior in both lizards and mammals will be extended. Recent studies with lizards and transgenic mice indicate that progesterone receptor is involved in the neuroendocrine control of male sexual behavior, and, in mammal, there is suggestive evidence that some of dopamine's effects on sexual behavior may be mediated by its interactions with the progesterone receptor. This grant aims to evaluate the generality of dopamine-progesterone receptor interactions across vertebrate taxa, to characterize the modulatory role of genotype on experiential effects, and to assess the independent contributions of genotypic sex vs. gonadal sex on sexual behavior and the brain. As work stemming from reptilian models has led to novel discoveries about mammalian systems, we anticipate that these studies will contribute important questions and hypotheses about the environmental and internal determinants of human sexual behavior.
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