Opioid Receptor Blockade Promotes Weight Loss and Improves the Display of Sexual Behaviors in Obese Zucker Female Rats

MARÍN-BIVENS, C. L. AND D. H. OLSTER. Opioid receptor blockade promotes weight loss and improves the display of sexual behaviors in obese Zucker female rats. PHARMACOL BIOCHEM BEHAV 63(3) 515–520, 1999.—Obese Zucker female rats are hyperphagic, overweight, infertile, and hyporesponsive to the inductive effects of ovarian steroid hormones on sexual behaviors. It has been postulated that endogenous opioid activity may contribute to their obesity and reproductive dysfunction. To test this hypothesis, ovariectomized, adult obese Zucker rats were treated with the opioid receptor antagonist, naltrexone, or saline prior to measurement of steroid-induced sexual behaviors, food intake, and body weight. In estradiol benzoate (EB)-treated rats, naltrexone injection increased the display of sexual receptivity (lordosis quotient, LQ: saline, 11 ± 10%; 5 mg/kg naltrexone, 54 ± 15%, p < 0.05) and also elicited proceptivity (PRO), which was never observed after saline injection. In EB plus progesterone-treated animals, naltrexone administration enhanced both sexual receptivity and proceptivity (LQ: saline, 17 ± 10%; 5 mg/kg naltrexone, 96 ± 3%; p < 0.05; PRO: saline, 3.0 ± 2.4 bouts/min; 5 mg/kg naltrexone, 45.3 ± 12 bouts/min; p < 0.01). Naltrexone injection also decreased 24-h food intake (saline, 24.2 ± 0.7 g; 5 mg/kg naltrexone, 17.6 ± 1.2 g; p < 0.05) and weight change (saline, + 7.3 ± 0.8 g; 5 mg/kg naltrexone, −4.5 ± 1.4 g, p < 0.01). Morphine treatment blocked these effects of naltrexone on sexual behaviors, food intake, and body weight. These data suggest that endogenous opioids contribute to hyperphagia, obesity, and behavioral hyporesponsiveness to ovarian steroid hormones in obese Zucker rats.