Interaction of naltrexone with postnatal administration of testosterone and estrogen on neurobehavioral sexual differentiation in rats

The present study examined whether some effects of gonadal sex hormones on neurobehavioral sexual differentiation might be mediated by endogenous opioids. Male and female pups were administered sesame oil, testosterone propionate (TP; 25 μg) or estradiol benzoate (EB; 10 μg) on postnatal Days 2 and 3. Half of each group was also administered naltrexone (N; 50 μg) twice daily on these two days. Females were studied for effects of the treatments on puberty. Males and females were studied in adulthood for open field behavior, daily water intake, and saccharin consumption and preference for 0.125, 0.25, and 0.50% saccharin solutions. TP treatment significantly delayed the date of vaginal opening, whereas EB treatment significantly accelerated the date. N treatment potentiated this effect of TP, but had no effect in EB treated females, nor did it influence the anovulatory sterility produced by both hormone treatments. N treatment alone had no effect on puberty in females or open field behavior of either sex. The drug produced an overall increase in female saccharin consumption and preference, but no effect was observed in males on these measures. Both TP and EB treatment produced marked increases in daily water consumption in females, an effect which was significantly attenuated by N treatment. Effects of both hormones on saccharin consumption were sex dependent and partially antagonized by N treatment. Finally, we observed a sex difference in daily water intake wherein females were found to consume approximately 20% more water on a body weight basis in a 24-hr period than males. Postnatal TP and EB treatment increased adult daily water consumption in females above the level of controls. This increase was partially antagonized by N. Treatment with N alone had no effect on female water consumption, but produced a small decrease in male consumption. Overall, these results provide preliminary evidence that some organizational effects of TP and EB on nonreproductive sex differences may be mediated by endogenous opioids.