Oleoylethanolamide effects on stress-induced alcohol consumption: a lipid at crossroads between stress, reward and neuroinflammation

The endocannabinoid system is involved in multiple drug-related behavior as well as in the stress response. The transient increase in endogenous cannabinoids as well as endocannabinoid-like molecules contributes to healthy adaptation to stress exposure. In this study, we tested the effect of systemic OEA treatment (10mg/kg) before or after social defeat (SD) on alcohol self-administration (SA). Mice were divided into non-stressed (EXP) and stressed mice (SD) and randomly assigned to a treatment condition (CTRL, OEA or 10OEA). Mice in the EXP/SD-OEA group received four doses before each SD encounter while mice in the EXP/SD-10OEA mice received 10 daily doses after stress exposure. Three weeks after SD, mice were trained to alcohol 20% (vol/vol) SA. Upon extinction, a cue-induced reinstatement test was performed. Our results showed that only multiple-dose chronic OEA treatment (SD-10OEA group) was effective in preventing the stress-induced increase in alcohol consumption observed in defeated mice. We did not observe any effects of OEA on relapse-like behavior. Altogether, these data suggest that exogenously increasing OEA levels counteracts the adverse effects of stress on alcohol drinking.