Binge-pattern alcohol exposure during puberty induces sexually dimorphic changes in genes regulating the HPA axis.
Maternal alcohol consumption during critical periods of fetal brain development leads to devastating long-term consequences on adult reproductive physiology, cognitive function, and social behaviors. However, very little is known about the long-term consequences of alcohol consumption during puberty, which is perhaps an equally dynamic and critical period of brain development. Alcohol abuse during adulthood has been linked with an increase in clinically diagnosed anxiety disorders, yet the etiology and neurochemical mechanisms of alcohol-induced anxiety behavior is unknown. In this study, we determined the effects of binge ethanol exposure during puberty on two critical central regulators of stress and anxiety behavior: corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). Our results showed that ethanol increased plasma corticosterone (CORT) levels in both sexes, yet binge-treated animals had significantly lower CORT levels than animals exposed to a single dose, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis habituated to the repeated stressful stimuli of ethanol. Binge ethanol exposure also significantly increased CRH and AVP gene expression in the paraventricular nucleus of males, but not females. Overall, our results demonstrate that binge ethanol exposure during puberty changes the central expression of stress-related genes in a sex-specific manner, potentially leading to permanent dysregulation of the HPA axis and long-term behavioral consequences.
Przybycien-Szymanska
Magdalena M
MM
Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Rao
Yathindar S
YS
Pak
Toni R
TR
D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D001127:Arginine Vasopressin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D002492:Central Nervous System Depressants / Q000506:poisoning*; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D000431:Ethanol / Q000506:poisoning*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000187:drug effects*
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D000431:Ethanol; D003346:Corticotropin-Releasing Hormone