Abstract
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.
Highlights
Oleoylethanolamide (OEA) is a bioactive lipid mediator that belongs to the fatty acid ethanolamide (FAE) family
To fill this knowledge gap, we evaluated the potential roles of OEA and PPAR-α in alcohol-seeking behavior and monitored the changes in OEA production during acute and chronic ethanol exposure
Because OEA reduces food intake through a peripheral mechanism, but reports exists about its ability to modulate central dopaminergic pathways, we studied the effects of OEA when injected centrally and in animals with chemical sensory deafferentation
Summary
Oleoylethanolamide (OEA) is a bioactive lipid mediator that belongs to the fatty acid ethanolamide (FAE) family. AEA and CB1 receptors have been shown to mediate some of the pharmacological and behavioral aspects of alcohol use (Basavarajappa & Hungund 2002; Rodríguez de Fonseca et al 2005; Ferrer et al 2007), the effects of non-cannabinoid FAEs such as OEA have been poorly characterized, and direct experimental evidence regarding the behavioral significance of the OEA–PPAR-α interaction on ethanol-related behaviors is still lacking To fill this knowledge gap, we evaluated the potential roles of OEA and PPAR-α in alcohol-seeking behavior (ethanol self-administration and relapse) and monitored the changes in OEA production during acute and chronic ethanol exposure
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