Discontinuous versus Continuous Drinking of Ethanol in Peripubertal Rats: Effect on 24-Hour Pattern of Hypophyseal-Gonadal Axis Activity and Anterior Pituitary Oxidative Stress

Abstract

Aims: Discontinuous (weekend) consumption of alcohol is common in adolescents and young adults. This study therefore assesses, in peripubertal male rats, the effect of discontinuous as compared to chronic feeding of ethanol or control liquid diet. Methods: Animals received an ethanol liquid diet (6.2 % w/v) starting on day 35 of life. Every week for 5 weeks, the discontinuous ethanol group received the ethanol diet for 3 consecutive days and the control liquid diet for 4 days. At the 5th week, 24 h after the last ethanol administration to the discontinuously ethanol-treated animals, rats were killed at 4-hour intervals beginning at 09.00 h. Chronically administered rats received the ethanol diet until immediately before study. Results: Disrupted 24-hour rhythmicity together with a significant nocturnal increase in plasma luteinizing hormone (LH), testosterone and prolactin (PRL) occurred in the discontinuous ethanol group. Plasma ethanol levels were undetectable at 24 h after the last ethanol treatment. In contrast, after chronic ethanol administration, plasma PRL was increased late in scotophase while LH and testosterone decreased; blood ethanol levels were 2-fold greater than those in discontinuously ethanol-administered rats killed immediately after ethanol withdrawal. Circulating testosterone positively correlated with LH levels in control rats only. Chronic administration of ethanol significantly augmented mean expression of pituitary nitric oxide synthase (NOS)-2, heme oxygenase (HO)-1, Per1 and Per2 genes and disrupted their diurnal rhythmicity. Decreased NOS-1 and NOS-2 expression during scotophase, together with suppression of the rhythm in Per1 and Per2 expression, were found in the discontinuous ethanol group. Conclusions: Abstinence after discontinuous drinking of alcohol in rats, as compared to chronic administration of ethanol, is accompanied by increases of plasma LH and testosterone, a greater PRL response and a less pronounced oxidative damage of the anterior pituitary.

An In Vitro Model of Human Acute Ethanol Exposure That Incorporates CXCR3- and CXCR4-Dependent Recruitment of Immune Cells

“…Of note, even with regular replacement of media in our cultures, it is likely that the effective concentration within PCLS is likely to be lower than 100mM as we have observed up to 30% decrease in effective concentration over 24 h due to evaporation in cell free wells (not shown). This is of interest because we may be incidentally mimicking physiological discontinuous exposure patterns caused by patterns of sleep or weekend consumption of alcohol, which are associated with reduced systemic oxidative stress but enhanced immune activation in animal models compared with continuous exposure (Fernandez-Mateos et al, 2012). However, we would need to compare maintained exposure and interrupted exposure using a perfusion delivery system to assess whether such patterns of exposure alter immune cell recruitment in the human system.…”