Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism.
Oleoylethanolamide (OEA) is a satiety factor that binds to the peroxisome proliferator-activated receptor-alpha (PPARα). This bioactive lipid mediator also acts as a homeostatic signal that controls multiple aspects of the physiological adaptations to alcohol exposure. OEA production is triggered by alcohol administration, contributes to the regulation of alcohol consumption and the acute motivational response to alcohol, and reduces the severity of somatic withdrawal symptoms.