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

(1) 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 r...

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Main Authors: Laura Sánchez-Marín, María Flores-López, Ana L. Gavito, Juan Suárez, Francisco Javier Pavón-Morón, Fernando Rodríguez de Fonseca, Antonia Serrano
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/3/593
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author Laura Sánchez-Marín
María Flores-López
Ana L. Gavito
Juan Suárez
Francisco Javier Pavón-Morón
Fernando Rodríguez de Fonseca
Antonia Serrano
author_facet Laura Sánchez-Marín
María Flores-López
Ana L. Gavito
Juan Suárez
Francisco Javier Pavón-Morón
Fernando Rodríguez de Fonseca
Antonia Serrano
author_sort Laura Sánchez-Marín
collection DOAJ
description (1) 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.
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spelling doaj.art-263da679e5ed4e248015a8036fbed2db2023-11-24T00:32:30ZengMDPI AGBiomedicines2227-90592022-03-0110359310.3390/biomedicines10030593Repeated Restraint Stress and Binge Alcohol during Adolescence Induce Long-Term Effects on Anxiety-like Behavior and the Expression of the Endocannabinoid System in Male RatsLaura Sánchez-Marín0María Flores-López1Ana L. Gavito2Juan Suárez3Francisco Javier Pavón-Morón4Fernando Rodríguez de Fonseca5Antonia Serrano6Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, SpainInstituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma Bionand, 29590 Málaga, Spain(1) 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.https://www.mdpi.com/2227-9059/10/3/593alcoholstressadolescenceendocannabinoid systemamygdalamedial prefrontal cortex
spellingShingle Laura Sánchez-Marín
María Flores-López
Ana L. Gavito
Juan Suárez
Francisco Javier Pavón-Morón
Fernando Rodríguez de Fonseca
Antonia Serrano
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
alcohol
stress
adolescence
endocannabinoid system
amygdala
medial prefrontal cortex
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic alcohol
stress
adolescence
endocannabinoid system
amygdala
medial prefrontal cortex
url https://www.mdpi.com/2227-9059/10/3/593
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