Adolescent alcohol exposure alters the central brain circuits known to regulate the stress response

Abstract

Adolescent alcohol exposure (AAE) may exert long-term effects on the adult brain. Here, we tested the hypothesis that the brain regions affected include the rat hypothalamic-pituitary-adrenal (HPA) axis. Specifically, we examined the consequences of AAE [postnatal days (PND) 28-42] on the HPA axis-related brain circuitry of male rats challenged with an intragastric (ig) administration of alcohol in young adulthood (PND 61-62). Adolescent rats were exposed to alcohol vapors, while controls did not receive the drug. The mean blood alcohol level in adolescence on PND 40 was 212.8±5.7 mg %. Using immunohistochemistry and in situ hybridization procedures, we measured signals for c-fos and corticotropin releasing factor (CRF) in the paraventricular nucleus (PVN) of the hypothalamus, as well as signals for c-fos and phenylethanolamine N-methyltransferase (PNMT) in the adrenergic brain stem regions (C1 and C2). PVN CRF mRNA expression was significantly blunted in AAE rats tested at PND 61-62, compared to their controls. These animals also displayed a significant increase in the mean number of PNMT-ir cells/brain stem section in the C2 area. Collectively, these results suggest that exposure to alcohol vapors during adolescence exerts long-term effects on the ability of the PVN to mount a response to an acute alcohol administration in young adulthood, possibly mediated by medullary catecholamine input to the PVN.

Figure 1

Exposure to intermittent alcohol vapors during adolescence blunts CRF mRNA expression in the PVN of young adult male rats administered an alcohol challenge (4.5 g/kg, via ig catheter), compared to air-exposed adolescent controls. A: Dark-field photomicrographs show coronal sections through the PVN 2 h after alcohol challenge in adulthood. Magnification, 100X; B: Mean ± SEM CRF mRNA expression (optical density as arbitrary units expressed as % of control) of 5 – 7 rats/treatment, ★: ★ p < 0.01.

Figure 2

Exposure to intermittent alcohol vapors during adolescence increases the number of PNMT immunoreactive cells in the C2 region of the brain stem of young adult rats administered an alcohol challenge (4.5 g/kg, via ig catheter), compared to controls. In addition, although not statistically significant, there was an increasing trend in the number of colocalized c-fos and PNMT immunoreactive cells. A: Double immunohistochemical procedure stained c-fos black nuclei and PNMT brown cytoplasm. Display panels compare the two conditions and the pictures were taken with a 20X dry objective (scale bar = 10 μm) and the inset a 40X dry objective; B: Mean ± SEM number of colocalized c-fos and PNMT (top) or PNMT (bottom) positive cells/section, n = 5 – 7 rats/treatment, ★: p < 0.05.