Pavon, Francisco JavierMarco, Eva MariaVazquez, MariamSanchez, LauraRivera, PatriciaGavito, AnaMela, VirginiaAlen, FranciscoDecara, JuanSuarez, JuanGine, ElenaLopez-Moreno, Jose AntonioChowen, JulieRodriguez-de-Fonseca, FernandoSerrano, AntoniaViveros, Maria Paz2016-11-152016-11-152016-09-23Pavón FJ, Marco EM, Vázquez M, Sánchez L, Rivera P, Gavito A, et al. Effects of Adolescent Intermittent Alcohol Exposure on the Expression of Endocannabinoid Signaling-Related Proteins in the Spleen of Young Adult Rats. PLoS ONE. 2016; 11(9):e0163752http://hdl.handle.net/10668/2525Intermittent 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.enAttribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/Peroxisome Proliferator-Activated ReceptorsProteinsSpleenInflammationRNA, MessengerAlcohol DrinkingAnimalsChemokine CX3CL1CytokinesDrinkingEndocannabinoidsEthanolInflammationresearch article27662369open accessConsumo de bebidas alcohólicasQuimiocina CX3CL1CitocinasIngestión de líquidosInflamaciónInterleucina-6Receptor cannabinoide CB1Factor de necrosis tumoral alfa10.1371/journal.pone.01637521932-6203PMC5035052