Exposure to alcohol during adolescence exerts long-term effects on stress response and the adult brain stress circuits

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis undergoes critical developments during adolescence. Therefore, stressors experienced during this period potentially have long-term effects on adult HPA axis function. We hypothesized that adolescent intermittent ethanol (AIE) exposure would affect adult HPA axis function, resulting in altered responses to an alcohol challenge in young adults or adults. To test these hypotheses, male rats were exposed to alcohol vapor for 6 h per day from post-natal day (PND) 28–42, then acutely challenged with alcohol intragastrically (3.2–4.5 g/kg) in young adults (PND 70) or adults (PND 90). Overall, we observed blunted HPA axis responses to an alcohol challenge due to AIE exposure. Specifically, AIE tended to inhibit the alcohol-challenge-induced increase in plasma corticosterone (CORT) concentrations in young adult and adult rats. As well, AIE significantly blunted the alcohol challenge-induced arginine vasopressin (Avp) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus of adult rats. Results of the present study are similar to what we have previously shown, that these changes in PVN responsiveness may result from AIE-induced alterations in adrenergic neurons in brain stem regions C1–C3 known to project to the PVN. AIE elevated the number of colocalized c-fos/phenylethanolamine N-methyltransferase (PNMT)-positive cell bodies in the C1 region of adult rats. Together, this data suggests that AIE exposure produces alterations in male HPA axis responsiveness to administration of an acute alcohol challenge that may be long-lasting.

Adolescent Ethanol Exposure Leads to Stimulus-Specific Changes in Cytokine Reactivity and Hypothalamic-Pituitary-Adrenal Axis Sensitivity in Adulthood

“…The work of Pak using a similar model of ethanol administration has shown sensitization of the axis response in males following adult ethanol challenge (Przybycien-Szymanska et al, 2010 , 2011 ). In contrast, a different study in which male adolescent rats received AIE and were challenged with ethanol in adulthood showed blunting of the axis response to later ethanol challenge (Allen et al, 2016 ). There are a number of factors that could account for this disparity.…”

“…In the third experiment, rats were given an acute ethanol challenge during adulthood to test for durable changes in HPA axis sensitivity to the same challenge(s) utilized during adolescence, and to provide a referent to other published studies (Przybycien-Szymanska et al, 2010 , 2011 ; Allen et al, 2016 ). Male rats ( n = 8–10 per group; N = 18) were given two cycles of intermittent ethanol exposure or vehicle intubations as described above.…”

“…In contrast, a more recent study showed that adolescent ethanol exposure (daily exposure to ethanol vapor for 6 h maintaining blood alcohol levels, BALs of 200 mg/dL) blunted the HPA axis response to adult ethanol challenge (3.2–4.5 g/kg intragastric (i.g. ); Allen et al, 2016 ). Though dose, route and frequency of ethanol exposure during adolescence are likely explanations for the differences between these studies, a more fundamental question regarding the potential for stressor-specific outcomes in adults with a history of adolescent ethanol exposure still remains.…”

Offspring of male rats exposed to binge alcohol exhibit heightened ethanol intake at infancy and alterations in T-maze performance

“…Illustrating this point, research has shown that ethanol exposure alters the response of the hypothalamic-pituitary-adrenal (HPA) axis (Rompala et al, 2016), one of the main components of the stress response. Acute ethanol exposure over-activates the response the axis, yet chronic, and often intermittent, ethanol exposure, blunts the subsequent stress-or EtOH-mediated activation of the axis (Lee et al, 2000;Allen et al, 2016). These altered response to stress may, in turn, have resulted in greater ethanol intake in the PE offspring.…”

Young alcohol binge drinkers have elevated blood endotoxin, peripheral inflammation and low cortisol levels: neuropsychological correlations in women

“…This hypothesis may indicate that young people who engage in regular patterns of alcohol binge intoxication are more vulnerable to the addictive effects of alcohol, although further research is clearly needed in this aspect. Interestingly, it has been recently shown that intermittent alcohol exposure in adolescent animals blunted the HPA axis over a long‐term period (Allen et al ). The decrease in cortisol levels could be reflecting the status of HPA axis activation; although to confirm this hypothesis, other elements of the axis must be measured.…”