Estradiol and progesterone alter ethanol-induced effects on μ-opioid receptors in specific brain regions of ovariectomized rats

This study was conducted to evaluate the effects of estradiol and progesterone on ethanol-induced alterations of mu-opioid receptor binding kinetics in specific brain regions. Female ovariectomized rats were injected with ethanol (3 g/kg, i.p.), estradiol (50 mu g/kg, s.c.) and/or progesterone (5 mg/kg, s.c.), or ethanol plus estradiol and/or progesterone daily for 7 days. Control animals received saline and olive oil. Brains were immediately removed and the cortex, hippocampus, hypothalamus, and midbrain were dissected and assayed for mu-opioid receptor binding kinetics. In the hypothalamus, ethanol alone and in combination with estradiol and/or progesterone significantly decreased B-max. Ethanol alone also decreased B-max in the midbrain and cortex. When administered with estradiol only, ethanol increased B-max and K-d in the hippocampus. The administration of estradiol alone and progesterone alone decreased B, in the hypothalamus, while not affecting B-max in any of the other brain regions. However, when estradiol and progesterone were combined, B-max, as well as K-d, increased in the cortex. Progesterone alone and in combination with estradiol also increased K-d in the midbrain. In addition, K-d significantly increased following administration of ethanol in combination with either of the hormones, or both, in the midbrain and cortex. These results clearly indicate that the female hormones modulate the effects of ethanol on binding kinetics of mu-opioid receptors in specific brain regions. The present findings may in part explain sex differences in alcohol effects.