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.

Figure 1. Effects of pubertal binge ethanol pre-treatments on plasma CORT levels in EtOH exposed adult animals.

Plasma corticosterone (CORT) levels 1.0 h post-injection of 3 g/kg EtOH in adult animals. Animals were treated during puberty with either saline (EtOH Naïve) or binge EtOH (EtOH pre-exposed). Adult animals were then treated with saline (open bars), acute EtOH (hatched bars) or binge EtOH (solid bars). Data are expressed as mean ± SEM CORT ng/ml. Dissimilar letters indicate a statistically significant difference between groups for all pairwise comparisons (P<0.05).

Figure 2. Effects of pubertal binge ethanol pre-treatments on CRH gene expression in the PVN of ethanol exposed adult rats.

CRH mRNA expression 1.0 h post-injection of 3 g/kg EtOH in adult animals. Animals were treated during puberty with either saline (EtOH Naïve) or binge EtOH (EtOH pre-exposed). Adult animals were then treated with saline (open bars), acute EtOH (hatched bars) or binge EtOH (solid bars). Data are expressed as mean ± SEM CRH mRNA copies/µg total RNA. Dissimilar letters indicate a statistically significant difference between groups for all pairwise comparisons (P<0.05).

Figure 3. Effects of pubertal binge ethanol pre-treatments on AVP gene expression in the PVN of ethanol exposed adult rats.

AVP mRNA expression 1.0 h post-injection of 3 g/kg EtOH in adult animals. Animals were treated during puberty with either saline (EtOH Naïve) or binge EtOH (EtOH pre-exposed). Adult animals were then treated with saline (open bars), acute EtOH (hatched bars) or binge EtOH (solid bars). Data are expressed as mean ± SEM AVP mRNA copies/µg total RNA. Dissimilar letters indicate a statistically significant difference between groups for all pairwise comparisons (P<0.05).

Figure 4. Effects of pubertal binge ethanol pre-treatments on AVP gene expression in the SON of ethanol exposed adult rats.

AVP mRNA expression 1.0 h post-injection of 3 g/kg EtOH in adult animals. Animals were treated during puberty with either saline (EtOH Naïve) or binge EtOH (EtOH pre-exposed). Adult animals were then treated with saline (open bars), acute EtOH (hatched bars) or binge EtOH (solid bars). Data are expressed as mean ± SEM AVP mRNA copies/µg total RNA. Dissimilar letters indicate a statistically significant difference between groups for all pairwise comparisons (P<0.05).