Altered stress responsiveness in adult rats exposed to ethanol in utero: neuroendocrine mechanisms.
In our first studies the activity of the hypothalamo-pituitary-adrenal (HPA) axis was found to be significantly greater in response to certain stressors, including ethanol, in adult rats exposed to ethanol as fetuses (fetal ethanol-exposed [FEE] rats) than in pair-fed-derived or normal controls. Stress responsiveness in FEE rats was examined further by measuring stress-induced analgesia after inescapable footshock. Analgesia was enhanced in adult FEE rats by a prolonged/intermittent naloxone-reversible form of footshock, but not by a brief/continuous naloxone-insensitive form, suggesting that the effect was opioid-mediated. Adult FEE rats showed greater analgesic and plasma corticosterone responses to morphine challenges than control rats. Preliminary results also indicated that when adult FEE rats were exposed daily to the intermittent footshock stress (10 min/day) they consumed significantly more ethanol than controls. Whether the altered stress responsiveness reflects fetal ethanol-induced effects on the development of the HPA axis was determined by measuring brain and plasma content of corticosterone in FEE and control neonates. At birth, in FEE pups, whole brain and plasma corticosterone levels are significantly raised. On postnatal day 7, when basal plasma corticosterone concentrations have attained normal values, FEE rats display blunted corticosterone responses to ethanol administration, indicating persistent effects of the fetal ethanol exposure despite its termination one week previously. The precise contribution of these neonatal hormonal alterations to the long-term effects of fetal ethanol exposure on stress responsiveness remains to be determined.
D000428:Alcohol Drinking; D000698:Analgesia; D000818:Animals; D001696:Biomechanical Phenomena; D001923:Brain Chemistry; D003345:Corticosterone / Q000032:analysis / Q000097:blood; D004597:Electroshock; D004702:Endocrine Glands / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D009020:Morphine / Q000494:pharmacology; D009420:Nervous System / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000503:physiopathology*
D000431:Ethanol; D009020:Morphine; D003345:Corticosterone