Attenuation of oleoylethanolamide-induced reduction of alcohol consumption in adult rats exposed intermittently to alcohol during adolescence

•SR141716A reduced alcohol consumption independently of an adolescent alcohol exposure.•OEA reduced alcohol consumption in adult rats without an adolescent alcohol exposure.•OEA did not affect alcohol consumption in rats with an adolescent alcohol exposure.•Co-treatment with OEA and SR141716A reduced alcohol intake. 5) The effect of co-treatment was attenuated in rats with adolescent alcohol exposure. Oleoylethanolamide (OEA) is an endogenous N-acylethanolamine that reduces both food and alcohol intake through the activation of peripheral sensory nerves in the gut. These effects are opposite to those of anandamide, a main endogenous cannabinoid type 1 receptor (CB1R) agonist. The present study aims to characterize the impact of intermittent and voluntary alcohol intoxications (using the two-bottle choice paradigm) during adolescence on inhibitory actions of OEA and the CB1R antagonist/inverse agonist SR141716A on voluntary alcohol intake in adulthood. In the present study we show that both OEA (5 mg/kg) and SR141716A (3 mg/kg) reduce alcohol drinking in adult rats using a two-bottle choice paradigm. These effects lasted for 24 h and were not additive when both compounds were co-administered. However, when OEA and SR141716A were administered to adult rats with a history of intermittent alcohol exposure during adolescence (from postnatal day 31 to 55), the effects of OEA were attenuated. Moreover, the co-administration of OEA and SR141716A was not as effective as the administration of SR141716A alone. These data suggest that adolescent exposure to alcohol alters the inhibitory actions of OEA on alcohol drinking, which results in the loss of a protective mechanism that might account for the long-term effects of alcohol exposure in the adolescence. The implications for the vulnerability to alcohol addiction is discussed.