Adolescent alcohol exposure alters the rat adult hypothalamic-pituitary-adrenal axis responsiveness in a sex-specific manner.

Exposure to alcohol during adolescence exerts long-term effects on the adult brain stress circuits, causing many changes that persist into adulthood. Here we examined the consequences of adolescent intermittent ethanol (AIE, administered from postnatal day (PND) 28-42) on the hypothalamic-pituitary-adrenal (HPA) axis-related brain circuitry of rats challenged with intragastric (ig) administration of alcohol in adulthood (PND 70-71). Both male and female adolescent rats were exposed to alcohol vapors, while controls did not receive the drug, to assess whether AIE alters adult alcohol response in a sex-specific manner. We demonstrated that AIE increased paraventricular nucleus (PVN) Avp mRNA levels during late (PND 42) but not middle (PND 36) adolescence in males. While an alcohol challenge administered to 70-71-day-old rats increased Crf mRNA levels in males and Avp mRNA levels in females, AIE blunted both effects. These results suggest that AIE produced long-lasting changes in the responsiveness of the HPA axis to a subsequent alcohol challenge in a sex-specific manner. Furthermore, AIE altered adrenergic brain stem nuclei involved in stress responses in adulthood, resulting in increased numbers of phenylethanolamine N-methyltransferase (PNMT) neurons in male C2 and female C1 regions. This tended to enhance activation of the male C2 nucleus upon alcohol challenge. Collectively, these results suggest that AIE exerts long-term effects on the ability of the PVN to respond to an alcohol challenge in adulthood, possibly mediated by catecholaminergic input from the brain stem to the PVN.