Genetic and experiential effects on dopaminergic systems

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Woolley, Sarah Cushing

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Successful reproduction requires the coordination of relevant sensory inputs with motivational and motor systems primed by sex steroid hormones to produce an appropriate hierarchical sequence of movements. Both behavioral and neural phenotypes can be altered by social interactions that, in turn, can produce long term changes in cellular activity and signaling, neural circuitry, and sexual behavior. There is considerable variability in the type and direction of neural and behavioral change in response to social interactions, and the degree of plasticity may depend on intrinsic or genetic individual differences. Dopaminergic systems modulate the expression of social and sexual behaviors in a number of vertebrate species and intrinsic differences in dopaminergic systems may underlie intrinsic individual differences in the display of sexual behavior. Here, I present data on how social interactions, genotype, and steroid hormones can affect dopamine synthesis in limbic and midbrain nuclei. I investigated this in three model systems including knockout mice and two related species of whiptail lizard. The knockout mice have a targeted deletion of the progesterone receptor and display higher mount and intromission frequencies than wild-type males. Male whiptail lizards (Cnemidophorus inornatus) have natural variation in the display of courtship behaviors: some males are more sexually vigorous than others. Finally, individuals of the parthenogenetic species C. uniparens, which arose from two hybridization events involving the sexual species C. inornatus, display both maleand female-like sexual behaviors depending on reproductive state. In contrast, C. inornatus females only display receptive behavior, and this only during when preovulatory. In all three species, individuals that displayed greater levels of mounting behaviors had greater numbers of cells expressing tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra pars compacta. In addition, in male whiptail lizards and the related parthenogen, dopamine production in the dorsal hypothalamus was correlated with the propensity to display mounting behaviors. Dopamine can increase the display of mounting behavior in mice as well as in male and parthenogenetic whiptail lizards. My dissertation indicates that not only is dopamine sufficient to elicit mounting behavior, but differences in dopamine production may contribute to individual differences in behavioral phenotype.