Region-specific gene expression changes associated to oleoylethanolamide-induced attenuation of alcohol self-administration

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA is targeting to achieve these effects have not been widely explored. Here, we tested the effects of OEA treatment during alcohol SA, extinction or previous to cue-induced reinstatement of alcohol seeking. In addition, we measured gene expression changes in the striatum and hippocampus of relevant receptors for alcohol consumption (DrD1, DrD2, CNR1, OPRM1) as well as immune-related proteins (IL-6, IL-1{beta}, TLR4) and the brain-derived neurotrophic factor (BDNF). Our results confirmed that when administered contingently, systemic OEA administration reduced alcohol SA and attenuated cue-induced reinstatement. Interestingly, we also observed that OEA treatment reduced the number of sessions needed for extinction of alcohol seeking. Biochemical analyses showed region-specific OEA dopaminergic and cannabinoid receptor gene expression alterations. Also, OEA treatment modulated the long-term immune response and increased BDNF expression. These results suggest that boosting OEA levels may be an effective strategy for reducing alcohol SA and preventing relapse.