Delayed but not Immediate Effects of Estrogen Curtail GABA-Mediated Feeding Responses Elicited from the Nucleus Accumbens Shell

The present study investigated immediate vs. delayed effects of estrogen replacement in ovariectomized (OVX) rats on hyperphagia elicited by GABA-A-agonist (muscimol) infusions into the nucleus accumbens shell (AcbSh). First, because intra-AcbSh muscimol-induced feeding has never been explored in OVX rats, a dose-effect curve was generated and compared to sham-operated males, the current point of reference in the literature. Muscimol (5, 10, 25, and 50 ng) increased food intake in both sexes, and both sexes reached the same asymptotic level of intake. Nevertheless, slopes of the linearized dose-effect functions for males and OVX females differed significantly, with females starting at a lower baseline and exhibiting a steeper slope. Next, the behavioral profiles of a behaviorally active, but non-maximal intra-AcbSh muscimol dose (25 ng) were examined in a separate group of OVX females at two time-points: immediately after injecting 17 β -estradiol 3-benzoate (EB) subcutaneously (5 μg), and 24 h post-EB. Delayed, but not immediate, EB pre-treatment strongly suppressed, but did not eliminate, muscimol-driven food intake. However, EB did not change non-food-directed behaviors such as locomotion or rearing. These results demonstrate that feeding mediated by intra-AcbSh GABA-A receptors is delimited by delayed, but not rapid, effects of estradiol.