Abstract
Intermittent alcohol exposure is a common pattern of alcohol consumption among adolescents and alcohol is known to modulate the expression of the endocannabinoid system (ECS), which is involved in metabolism and inflammation. However, it is unknown whether this pattern may have short-term consequences on the ECS in the spleen. To address this question, we examined the plasma concentrations of metabolic and inflammatory signals and the splenic ECS in early adult rats exposed to alcohol during adolescence. A 4-day drinking in the dark (DID) procedure for 4 weeks was used as a model of intermittent forced-alcohol administration (20%, v/v) in female and male Wistar rats, which were sacrificed 2 weeks after the last DID session. First, there was no liver damage or alterations in plasma metabolic parameters. However, certain plasma inflammatory signals were altered according to sex and alcohol exposition. Whereas fractalkine [chemokine (C-X3-C motif) ligand 1] was only affected by sex with lower concentration in male rats, there was an interaction between sex and alcohol exposure in the TNF-α and interleukin-6 concentrations and only female rats displayed changes. Regarding the mRNA and protein expression of the ECS, the receptors and endocannabinoid-synthesizing enzymes were found to be altered with area-specific expression patterns in the spleen. Overall, whereas the expression of the cannabinoid receptor CB1 and the nuclear peroxisome proliferator-activated receptor PPARα were lower in alcohol-exposed rats compared to control rats, the CB2 expression was higher. Additionally, the N-acyl-phosphatidylethanolamine-specific phospholipase D expression was high in female alcohol-exposed rats and low in male alcohol-exposed rats. In conclusion, intermittent alcohol consumption during adolescence may be sufficient to induce short-term changes in the expression of splenic endocannabinoid signaling-related proteins and plasma pro-inflammatory cytokines in young adult rats with a strong sexual dimorphism. The potential impact of these alterations in early adulthood remains to be elucidated.
Highlights
Alcohol is the most commonly used addictive drug in our society, and its consumption is increasing among young people and adolescents, becoming a major public health concern
Alcohol consumption is linked to the immune system affecting the expression of several inflammatory signals and other signaling systems closely related to inflammatory responses such as the endocannabinoid system (ECS)
A two-way analysis of variance (ANOVA) revealed a main effect of time of alcohol exposure on the blood ethanol concentration (BEC) (F1,28 = 30.06, p
Summary
Alcohol is the most commonly used addictive drug in our society, and its consumption is increasing among young people and adolescents, becoming a major public health concern. Whereas numerous studies have demonstrated that heavy episodic or binge drinking is able to modulate the production of inflammatory mediators [4,5], acute and moderate alcohol consumption have an inhibitory effect on the immune response by down-regulating the production and release of pro-inflammatory cytokines [6,7,8,9]. (e.g., interleukin-1 beta [IL-1β], IL-6 and tumor necrosis factor alpha [TNF-α]), and increases the secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10) [10] These immunosuppressive and anti-inflammatory effects were initially observed using the plant-derived cannabinoid delta-9-tetrahidrocannabinol (THC) [16] and subsequently with endocannabinoids [17,18]. The present study in rats was designed to investigate the effects on the splenic ECS-related proteins in young adult rats after an intermittent alcohol exposure during adolescence because early adulthood appears to be a critical period to consolidate addictive behaviors. We have analyzed relevant inflammatory mediators and metabolic parameters in the plasma and liver of these animals to detect inflammatory processes
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