Oleoylethanolamide attenuates cocaine-primed reinstatement and alters dopaminergic gene expression in the striatum

• Published in: Behavioral and brain functions Vol. 19; no. 1; pp. 8 - 11
• Main Authors: González-Portilla, Macarena, Mellado, Susana, Montagud-Romero, Sandra, Rodríguez de Fonseca, Fernando, Pascual, María, Rodríguez-Arias, Marta
• Format: Journal Article
• Language: English
• Published: England BioMed Central 24.05.2023; BMC
• Subjects: Animals; Brain research; Cannabinoid receptors; Cannabinoids; Cocaine; Cocaine - pharmacology; Dopamine; Dopamine D1 receptors; Dopamine D2 receptors; Drug dosages; Extinction; Gene Expression; Hippocampus; Male; Mice; Narcotics; Neostriatum; Neurotransmission; Oleic acid; Oleoylethanolamide; Opioid receptors; Receptors, Cannabinoid; Reinstatement; Substance abuse treatment; Cocaine; Dopamine; Oleoylethanolamide; Gene expression; Reinstatement
• ISSN: 1744-9081; 1744-9081
• DOI: 10.1186/s12993-023-00210-1

The lipid oleoylethanolamide (OEA) has been shown to affect reward-related behavior. However, there is limited experimental evidence about the specific neurotransmission systems OEA may be affecting to exert this modulatory effect. The aim of this study was to evaluate the effects of OEA on the rewarding properties of cocaine and relapse-related gene expression in the striatum and hippocampus. For this purpose, we evaluated male OF1 mice on a cocaine-induced CPP procedure (10 mg/kg) and after the corresponding extinction sessions, we tested drug-induced reinstatement. The effects of OEA (10 mg/kg, i.p.) were evaluated at three different timepoints: (1) Before each cocaine conditioning session (OEA-C), (2) Before extinction sessions (OEA-EXT) and (3) Before the reinstatement test (OEA-REINST). Furthermore, gene expression changes in dopamine receptor D1 gene, dopamine receptor D2 gene, opioid receptor µ, cannabinoid receptor 1, in the striatum and hippocampus were analyzed by qRT-PCR. The results obtained in the study showed that OEA administration did not affect cocaine CPP acquisition. However, mice receiving different OEA treatment schedules (OEA-C, OEA-EXT and OEA-REINST) failed to display drug-induced reinstatement. Interestingly, the administration of OEA blocked the increase of dopamine receptor gene D1 in the striatum and hippocampus caused by cocaine exposure. In addition, OEA-treated mice exhibited reduced striatal dopamine receptor gene D2 and cannabinoid receptor 1. Together, these findings suggest that OEA may be a promising pharmacological agent in the treatment of cocaine use disorder.