The ovarian hormones, estradiol (E) and progesterone (P) facilitate the expression of sexual behavior in female rats. E and P mediate many of these behavioral effects by binding to their respective intracellular receptors in specific brain regions. Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro. Previously, our lab has shown that SRC-1 and CBP modulate estrogen receptor (ER)-mediated induction of progestin receptor (PR) gene expression in the ventromedial nucleus of the hypothalamus (VMN) and hormone-dependent sexual receptivity in female rats. Female sexual behaviors can be activated by high doses of E alone in ovariectomized rats, and thus are believed to be ER-dependent. However, the full repertoire of female sexual behavior, in particular, proceptive behaviors such as hopping, darting and ear wiggling, are considered to be PR-dependent. In the present experiments, the function of SRC-1 and CBP in distinct ER- (Exp. 1) and PR- (Exp. 2) dependent aspects of female sexual behavior was investigated. In Exp. 1, infusion of antisense oligodeoxynucleotides to SRC-1 and CBP mRNA into the VMN decreased lordosis intensity in rats treated with E alone, suggesting that these coactivators modulate ER-mediated female sexual behavior. In Exp. 2, antisense to SRC-1 and CBP mRNA around the time of P administration reduced PR-dependent ear wiggling and hopping and darting. Taken together, these data suggest that SRC-1 and CBP modulate ER and PR action in brain and influence distinct aspects of hormone-dependent sexual behaviors. These findings support our previous studies and provide further evidence that SRC-1 and CBP function together to regulate ovarian hormone action in behaviorally-relevant brain regions.

Compulsive binge eating is a hallmark of binge eating disorder and bulimia nervosa and is implicated in some obesity cases. Eating disorders are sexually dimorphic, with females more often affected than males. Animal models of binge-like eating based on intermittent access to palatable food exist; but, little is known regarding sex differences or individual vulnerability in these models with respect to the reinforcing efficacy of food, the development of compulsive- and binge-like eating, or associated changes in whole-body metabolism or body composition. Adolescent male (n = 24) and female (n = 32) Wistar rats were maintained on chow or a preferred, high-sucrose, chocolate-flavored diet in continuous or intermittent, extended access conditions. Body weight and composition, intake, fixed- and progressive-ratio operant self-administration, and whole body energy expenditure and respiratory exchange ratios were measured across an 11-week study period. Subgroup analyses were conducted to differentiate compulsive-like "high responder" intermittent access rats that escalated to extreme progressive-ratio self-administration performance vs. more resistant "low responders." Female rats had greater reinforcing efficacy of food than males in all diet conditions and were more often classified as "high responders". In both sexes, rats with intermittent access showed cycling of fuel substrate utilization and whole-body energy expenditure. Further, "high-responding" intermittent access female rats had especially elevated respiratory exchange ratios, indicating a fat-sparing phenotype. Future studies are needed to better understand the molecular and neurobiological basis of the sex and individual differences we have observed in rats and their translational impact for humans with compulsive, binge eating disorders.

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