| Autor: |
González-Portilla M; Department of Psychobiology, Faculty of Psychology, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain., Montagud-Romero S; Department of Psychobiology, Faculty of Psychology, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain., Mellado S; Department of Physiology, School of Medicine, Universitat de Valencia, Avda. Blasco Ibáñez 15, 46010 Valencia, Spain., de Fonseca FR; Mental Health Clinical Management Unit, Institute of Biomedical Research of Malaga-IBIMA, Regional University Hospital of Málaga, 29010 Málaga, Spain.; Atención Primaria, Cronicidad y Promoción de la Salud, Red de Investigación en Atención Primaria de Adicciones (RIAPAD) Rd21/0009/0005/0003, Valencia, Spain., Pascual M; Department of Physiology, School of Medicine, Universitat de Valencia, Avda. Blasco Ibáñez 15, 46010 Valencia, Spain., Rodríguez-Arias M; Department of Psychobiology, Faculty of Psychology, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain.; Atención Primaria, Cronicidad y Promoción de la Salud, Red de Investigación en Atención Primaria de Adicciones (RIAPAD) Rd21/0009/0005/0003, Valencia, Spain. |
| Abstrakt: |
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 targets 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, Oprm) as well as immune-related proteins (Il-6, Il-1β, 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 the extinction of alcohol seeking. Biochemical analyses showed that OEA induced gene expression changes in dopamine and cannabinoid receptors in the striatum and hippocampus. In addition, 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. |
