Characterizing the ontogeny of ethanol-associated increases in corticosterone.
The following experiments were conducted as adjuncts to previous work in an effort to characterize the ontogenetic profile of the elevations in corticosterone after ethanol challenge. In Experiment 1, female and male Sprague-Dawley rats were administered intraperitoneally either a 1.5- or a 4.5-g/kg dose of ethanol on postnatal day (PND) 16, 26, 36, or 56. Blood samples were collected at 40, 80, or 160 min after ethanol injection and analyzed by means of radioimmunoassay for corticosterone levels and correlated with brain alcohol levels (BrALs) determined from brain samples collected at the same time intervals. In Experiment 2, the ethanol dose was varied ontogenetically to equate functional impairment across age, with the use of intraperitoneal doses of ethanol of 3.2, 2.6, or 2.2 g/kg, to induce equivalent amounts of ethanol-induced motor impairment in infant (PND 22), adolescent (PND 28), or adult (PND 60) rats, respectively. Animals were tested on a swim task 15 min after injection, with blood and brain samples collected immediately after the swim and analyzed for corticosterone levels and BrALs as in Experiment 1. Reminiscent of previous reports of an age-related increase in sensitivity to the hypnotic and motor-impairing effects of ethanol, the corticosterone response to an ethanol challenge increased at least through adolescence, with sex differences emerging by PND 26 and becoming more pronounced in adulthood. To the extent that corticosterone release is involved in the reinforcing effects of drugs, ontogenetic differences in the response of the hypothalamic-adrenal-pituitary (HPA) axis to ethanol could contribute to the excessive alcohol consumption often observed during adolescence.
Silveri
Marisa M
MM
Department of Psychiatry, Harvard Medical School, and Cognitive Neuroimaging Laboratory, McLean Hospital, Belmont, MA 02478, USA. msilveri@mclean.harvard.edu
Spear
Linda Patia
LP
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D003345:Corticosterone