This is a proposal for the continuation of a Research Scientist Development Award, now called an Independent Scientist Award (K02). During the first 4 years of this award the applicant's research program has expanded significantly. The applicant initiated a new line of research involving new collaborations and new technical skills. This program takes advantage of the laboratory mouse as a model system to study behavioral neuroendocrinology. The advantages that the mouse offers are the richness of its behavioral repertoire coupled with a superior knowledge of its genetics, and the ability to design and produce genetically engineered animals. The K02 award allowed the applicant to receive significant new training in neuro- and molecular biological techniques. The applicant's interest in sexual behaviors and the role of aromatization of androgen to estrogen in the activation of these behaviors lead her to begin working with the estrogen receptor alpha knockout mouse (ERaKOs). Her work to date has revealed that although sexual behavior and social preferences are deficient in ERaKO males and females, treatment with the dopamine agonist apomorphine can reinstate normal behavior. This finding challenges the dogma that aromatized estrogens masculinize brain development during the prenatal period. To further evaluate the role of steroid receptors in activation of sexual behavior the PI has obtained several additional KO mice; including the estrogen receptor beta knockout and Tfm mice (androgen receptor knockouts). During the upcoming K02 grant period the PI will examine the molecular bases for sexual behavior using a variety of approaches. These include; 1) in vivo microdialysis to examine neural catecholamine responses to nitric oxide and sexual encounters; 2) the use of high-density DNA arrays to monitor gene expression in response to hormones and/or behavioral interactions; and 3) training in molecular mouse genetics. The K02 award is extremely valuable since it frees the PI from much of her administrative and teaching responsibilities. This allows her to spend significant amounts of time in colleagues' laboratories learning new techniques and focus her energy on running her own program.
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