The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Neuroscience. 2013 Apr 3;235:174-86. doi: 10.1016/j.neuroscience.2012.12.069. Epub 2013 Jan 18.
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.
青春期接触酒精会对成年人大脑应激回路产生长期影响，导致许多变化持续到成年期。在这里，我们研究了青春期间歇性乙醇（AIE，从出生后第 28-42 天开始给药）对成年期（PND 70-71）经胃内（ig）给予酒精挑战的大鼠下丘脑-垂体-肾上腺（HPA）轴相关脑回路的影响。雄性和雌性青春期大鼠都暴露于酒精蒸气中，而对照组没有接受药物治疗，以评估 AIE 是否以性别特异性的方式改变成年期的酒精反应。我们证明，AIE 在雄性中增加了室旁核（PVN）Avp mRNA 水平在晚期（PND 42）但不在中期（PND 36）青春期。虽然给予 70-71 天大的大鼠酒精挑战会增加雄性中的 Crf mRNA 水平和雌性中的 Avp mRNA 水平，但 AIE 会削弱这两种作用。这些结果表明，AIE 以性别特异性的方式对 HPA 轴对随后的酒精挑战的反应产生了持久的变化。此外，AIE 改变了成年期参与应激反应的肾上腺素能脑干核，导致雄性 C2 和雌性 C1 区域的苯乙醇胺 N-甲基转移酶（PNMT）神经元数量增加。这往往会增强雄性 C2 核在酒精挑战时的激活。总的来说，这些结果表明，AIE 对 PVN 对成年期酒精挑战的反应能力产生长期影响，可能是通过来自脑干的儿茶酚胺能传入对 PVN 的作用介导的。
