RT Journal Article T1 Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats. A1 Sanchez-Marin, Laura A1 Flores-Lopez, Maria A1 Gavito, Ana L A1 Suarez, Juan A1 Pavon-Moron, Francisco Javier A1 Rodriguez-de-Fonseca, Fernando A1 Serrano, Antonia K1 Adolescence K1 Alcohol K1 Amygdala K1 Endocannabinoid system K1 Medial prefrontal cortex K1 Stress AB Background: Negative experiences during adolescence increase the vulnerability to develop mental disorders later in life. A better understanding of the mechanisms underlying these long-term alterations could help to identify better therapeutic interventions. (2) Methods: Adolescent male Wistar rats were used to explore the effects of repeated stress and alcohol exposure on anxiety-like behaviors, plasma corticosterone levels and the gene expression of the endocannabinoid system (ECS) and other relevant signaling systems (glutamatergic, corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY)) in the amygdala and the medial prefrontal cortex (mPFC). (3) Results: Overall, both stress and alcohol induced anxiety-like behaviors, but only the alcohol-exposed rats displayed increased plasma levels of corticosterone. In the amygdala, there was a general deficit in the gene expression of the ECS and increases in the mRNA levels of certain subunits of glutamate receptors. Interestingly, there were significant interaction effects between stress and alcohol on the expression of the NMDA receptor subunits. In addition, increased mRNA levels of the CRH receptor were observed in alcohol-exposed rats. In the mPFC, alcohol exposure was associated with an increase in the gene expression of the ECS. By contrast, the combination of stress and alcohol produced opposite effects. (4) Conclusions: In summary, early stress and alcohol exposure induced long-term anxiety-like behavior in male rats but different mechanisms are involved in these maladaptive changes in the brain. PB MDPI SN 2227-9059 YR 2022 FD 2022-03-03 LK http://hdl.handle.net/10668/20823 UL http://hdl.handle.net/10668/20823 LA en NO Sánchez-Marín L, Flores-López M, Gavito AL, Suárez J, Pavón-Morón FJ, de Fonseca FR, et al. Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male Rats. Biomedicines. 2022 Mar 3;10(3):593 NO This research was supported by the following grants: Subprograma Redes Temáticas RETICs (Red de Trastornos Adictivos RD16/0017/0001) funded by Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO) and European Regional Development Funds/European Social Fund (ERDF/ESF); Proyectos de Investigación en Salud (PI17/02026, PI19/00886, PI19/01577, DTS19/00125 and PI20/01399) funded by ISCIII, MINECO and ERDF/ESF; Proyectos de Investigación en Drogodependencias (2017I043 and 2018I044, 2018I033) funded by Delegación del Gobierno para el Plan Nacional sobre Drogas, Ministerio de Sanidad and ERDF/ESF; and Grupos PAIDI (CTS-433 and CTS-1052) funded by Consejería de Economía, Innovación y Ciencia, Junta de Andalucía and ERDF-EU. F.J.P.-M. and A.S. hold a “Miguel Servet II” research contract from ISCIII and ERDF-EU (CPII19/00022 and CPII19/00031, respectively). DS RISalud RD Apr 20, 2025