Browsing by Subject "Preoptic area"
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Item Estrogen and the aging brain of male rats(2016-12) Nutsch, Victoria Lynn; Dominguez, Juan M.; Gore, Andrea C., 1964-; Hofmann, Hans; Cummings, Molly; Gonzales, RuebenGonadal steroid hormones exert an influence on many aspects of neurobiology in men, including memory, learning and sexual dysfunction. Though testosterone is the main circulating gonadal steroid hormone in males, estradiol is also important, and together these hormones play complementary roles. While the specific roles of estrogen have been studied to some extent in young adults, little is known during aging, when sexual behavior can become impaired. I used a rodent model to examine estradiol’s role in sexual behavior and gene expression in 3 regions, selected for their importance in behavioral neuroendocrine functions and high concentrations of estrogen receptors: the medial preoptic area (mPOA), medial amygdala (MeA), and bed nucleus of the stria terminalis (BnST). My studies focused first on how age and sexual experience affects expression and activation of estrogen receptor α (ERα) and androgen receptor (AR) after sexual behavior in aging intact males. Quantification of neurons expressing hormone receptors in the mPOA revealed that neither ERα nor androgen receptor (AR) showed an age-related change in expression in the mPOA. While both ERα and AR were activated after copulation, the age-related changes were specific to ERα in the central mPOA. There were only mild deficits in sexual behavior. Serum estradiol was also elevated in both aged and copulating animals, but estradiol concentrations only correlated with sexual behavior in aged animals. In a second study, I determined how hormone deprivation (castration) and replacement with estradiol caused changes to gene expression in the mPOA, BnST and MeA. Each region had unique patterns of gene expression in response to aging and estradiol treatment. The mPOA only had changes in expression as a result of hormone administration, while the BnST had primarily age-related changes. The MeA had the greatest number of affected genes, mainly interactions between estradiol treatment and aging. These studies emphasize the importance of estradiol in aging males, and the need for continued study on its role in neuroendocrine and sexual function.Item The role of the preoptic area in response to cocaine(2016-05) Will, Ryan Gregory; Dominguez, Juan M.; Marinelli, Michela; Duvauchelle, Christine L; Gore, Andrea C; Jones, Theresa A; Monfils, Marie HThe preoptic area of the hypothalamus is ideally suited to modulate the behavioral and neural response to drugs of abuse such as cocaine. The preoptic area is broken up into two major subregions the medial preoptic area (mPOA) and the lateral preoptic area (LPO), both of which send dense projections to mesolimbic dopamine system. Specifically, both project to the ventral tegmental area (VTA), a brain region implicated in drug-associated reward. Previous work has demonstrated the mPOA is involved in the behavioral and neural response to cocaine in female rats, however the mechanism through which the mPOA modulates response to cocaine is unclear. Whether or not the mPOA also plays a role in response to cocaine in male rats is still not clear. Furthermore the role of the adjacent LPO in response to cocaine is unexplored, despite its anatomical relationship to the VTA and involvement in intracranial self-stimulation. Here I demonstrate that estradiol acts in the mPOA of female rats to modulate response to cocaine. Specifically, microinjections of estradiol directly into the mPOA one day prior to cocaine administration increase cocaine-induced dopamine levels in the nucleus accumbens. The mPOA is also involved in the behavioral regulation of response to cocaine in male rats, as mPOA lesions enhanced cocaine-induced locomotion and reward. Finally, activation of the LPO, with pharmacology or chemogenetics, potentiates reinstatement of cocaine seeking, an animal model of drug relapse. Together these results demonstrate that the preoptic area as a whole is involved in the regulation of the neural and behavioral response to cocaine and shed light on underlying regulatory mechanisms.