Binge-Pattern Alcohol Exposure during Puberty Induces Long-Term Changes in HPA Axis Reactivity

Abstract

Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH) treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis, as manifested by alterations in corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP), and corticosterone (CORT) during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

Ethanol-related alterations in gene expression patterns in the developing murine hippocampus

“…It is important to understand the molecular mechanism behind the harmful effects of ethanol gene expression profiling. Several investigations have already been reported which tried to unveil the mechanisms of ethanol-induced gene expression alteration in different aspects [17][18][19][20][21]. But the alcohol-regulated genes and their associated biological pathways have not yet been completely elucidated.…”

Clock genes × stress × reward interactions in alcohol and substance use disorders

“…Chronic alcohol exposure and alcohol bingeing in rodents influence the glucocorticoid feedback mechanism, mediated via glucocorticoid-responsive element (GRE) sites of the CRH promoter impairing CRH activity (Przybycien-Szymanska, Mott, & Pak, 2011; Przybycien-Szymanska, Mott, Paul, Gillespie, & Pak, 2011; Przybycien-Szymanska, Rao, & Pak, 2010; Spanagel et al, 2014). Intermittent access to alcohol also results in CRH increase in rhesus macaques (Schwandt et al, 2010), and functional variation of the CRH gene increases stress-induced alcohol consumption in non-human primates (Barr, 2013; Barr et al, 2009).…”

Repeated Binge-Like Ethanol Administration During Adolescence cause Decreased C-Fos Immunoreactivity in Amygdala and Arcuate Nucleus in Adult Sprague-Dawley Rats

“…Animal research has provided consistent evidence that binge-like ethanol exposure during this period causes long-lasting neuroadaptive changes in neural pathways that are critically involved in the neurobehavioral responses to ethanol (Lerma-Cabrera et al, 2013;Przybycien-Szymanska et al, 2011;Logrip et al, 2013), increases the risk of ethanol consumption and preference during adulthood, and promotes inhibition of molecular and cellular neuroadaptations (Pascual et al), in adult rats. These adaptations led to the hypothesis that long-term plasticity is one important underlying mechanism involved in addiction (Nestler, 2004).…”