Effects of intracerebroventricular leptin administration on feeding and sexual behaviors in lean and obese female Zucker rats

Obese Zucker rats (fa/fa) are characterized by inadequate leptin signaling caused by a mutation in the leptin receptor gene. Obese Zucker females are infertile and hyporesponsive to the inductive effects of ovarian hormones o n sexual behaviors. Leptin treatment reverses aspects of reproductive dysfu nction due to perturbations in energy balance in other animal models. Our f irst experiment tested the hypothesis that intracerebroventricular (icv) le ptin administration would enhance the display of sexual behaviors in obese Zucker females. A second experiment compared lean and obese Zucker females' responses to leptin, during fed and fasted conditions. Ovariectomized (OVX ) Zucker rats were implanted with lateral ventricular cannulae. In Experime nt 1, fasted, obese females received estradiol benzoate, progesterone, and icy injections of 3, 18, or 36 mu g murine leptin or vehicle. Leptin admini stration reduced food intake, but did not enhance sexual behaviors. In Expe riment 2, steroid-replaced, OVX lean and obese females (from a different so urce than those in Experiment 1) received icy injections of vehicle or 3 or 36 mu g leptin under fed and fasted conditions. Leptin treatment reduced f ood intake and weight gain in the fed, but not the fasted, condition in bot h genotypes. Sexual receptivity and locomotion were not affected, but icy l eptin injections reduced preceptive behaviors in ad libitum-fed rats. These data confirm previous reports that centrally administered leptin decreases food intake and weight gain in obese Zucker rats; results from Experiment 2 suggest that lean and obese females are similarly responsive to these act ions of leptin. Contrary to our hypothesis, leptin treatment did not stimul ate sexual behaviors; rather, the hormone appears to inhibit the display of sexual proceptivity in ad libitum-fed lean and obese Zucker female rats. ( C) 2000 Academic Press.