Effect of chronic estrogen on the skin temperature response to naloxone in morphine-dependent rats

It is well documented that opioids and sex steroids modify body temperature in the rat. We have previously reported that the temperature responses to naloxone in the morphine-dependent rat was more pronounced in the female than in the male rat. In addition, ovariectomy but not castration resulted in altered temperature responses in the morphine-dependent rat, which suggests a role for estrogen in modifying the temperature responses. This study was designed to evaluate the effect of sex steroid hormones on the surge in tail skin temperature associated with administration of naloxone to morphine-dependent female rats. Ovariectomized female rats were treated with estrogen (0.5 mg pellet), progesterone (5 mg pellet), or the combined therapy for 21 days. Administration of naloxone to these morphine-dependent rats resulted in a 5.9 ± 0.5 °C rise in tail skin temperature in the placebo control rats and 5.7 ± 0.5 °C in the progesterone-treated group; however, there was a significantly reduced elevation in tail skin temperature of 3.1 ± 1.0 °C and 2.9 ± 1.0 °C in the estrogen and estrogen–progesterone treated groups. Body weights also were significantly depressed in the estrogen-treated groups. In a subsequent study, the effects of several doses of chronic estrogen treatment were evaluated (0.1–50 mg pellets). The elevation of tail skin temperature in response to administration of naloxone to morphine-dependent rats was significantly reduced at all doses of estrogen when compared with placebo-treated controls. The degree of attenuation of the surge in tail skin temperature and the increases in uterine and anterior pituitary weights were similar in all five estrogen-treated groups despite the wide range of serum estrogen levels observed. The only apparent dose–response effect observed with the five levels of estrogen treatment was the reduction of body weight. Collectively, these results suggest that chronic estrogen, and not progesterone, replacement attenuates the rise in tail skin temperature observed in the morphine-dependent rat following administration of naloxone.