Cargando…
Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return
Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470908/ https://www.ncbi.nlm.nih.gov/pubmed/34572345 http://dx.doi.org/10.3390/biomedicines9091161 |
_version_ | 1784574320643670016 |
---|---|
author | Brancato, Anna Castelli, Valentina Lavanco, Gianluca Tringali, Giuseppe Micale, Vincenzo Kuchar, Martin D’Amico, Cesare Pizzolanti, Giuseppe Feo, Salvatore Cannizzaro, Carla |
author_facet | Brancato, Anna Castelli, Valentina Lavanco, Gianluca Tringali, Giuseppe Micale, Vincenzo Kuchar, Martin D’Amico, Cesare Pizzolanti, Giuseppe Feo, Salvatore Cannizzaro, Carla |
author_sort | Brancato, Anna |
collection | PubMed |
description | Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress; (2) stress-axis functionality; and (3) dopaminergic and glutamatergic neuroadaptation in the NAc. We also assess the potential effects of the non-intoxicating phytocannabinoid cannabidiol, to counteract (or reverse) the development of detrimental consequences of binge-like alcohol exposure. Our results show that adolescent binge-like alcohol exposure alters the sensitivity to positive stimuli, exerts social and novelty-triggered anxiety-like behaviour, and passive stress-coping during early and prolonged withdrawal. In addition, serum corticosterone and hypothalamic and NAc corticotropin-releasing hormone levels progressively increase during withdrawal. Besides, NAc tyrosine hydroxylase levels increase at late withdrawal, while the expression of dopamine transporter, D1 and D2 receptors is dynamically altered during binge and withdrawal. Furthermore, the expression of markers of excitatory postsynaptic signaling—PSD95; Homer-1 and -2 and the activity-regulated spine-morphing proteins Arc, LIM Kinase 1 and FOXP1—increase at late withdrawal. Notably, subchronic cannabidiol, during withdrawal, attenuates social- and novelty-induced aversion and passive stress-coping and rectifies the hyper-responsive stress axis and NAc dopamine and glutamate-related neuroplasticity. Overall, the exposure to binge-like alcohol levels in adolescent rats makes the NAc, during withdrawal, a locus minoris resistentiae as a result of perturbations in neuroplasticity and in stress-axis homeostasis. Cannabidiol holds a promising potential for increasing behavioural, neuroendocrine and molecular resilience against binge-like alcohol harmful effects. |
format | Online Article Text |
id | pubmed-8470908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84709082021-09-27 Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return Brancato, Anna Castelli, Valentina Lavanco, Gianluca Tringali, Giuseppe Micale, Vincenzo Kuchar, Martin D’Amico, Cesare Pizzolanti, Giuseppe Feo, Salvatore Cannizzaro, Carla Biomedicines Article Binge alcohol consumption among adolescents affects the developing neural networks underpinning reward and stress processing in the nucleus accumbens (NAc). This study explores in rats the long-lasting effects of early intermittent exposure to intoxicating alcohol levels at adolescence, on: (1) the response to natural positive stimuli and inescapable stress; (2) stress-axis functionality; and (3) dopaminergic and glutamatergic neuroadaptation in the NAc. We also assess the potential effects of the non-intoxicating phytocannabinoid cannabidiol, to counteract (or reverse) the development of detrimental consequences of binge-like alcohol exposure. Our results show that adolescent binge-like alcohol exposure alters the sensitivity to positive stimuli, exerts social and novelty-triggered anxiety-like behaviour, and passive stress-coping during early and prolonged withdrawal. In addition, serum corticosterone and hypothalamic and NAc corticotropin-releasing hormone levels progressively increase during withdrawal. Besides, NAc tyrosine hydroxylase levels increase at late withdrawal, while the expression of dopamine transporter, D1 and D2 receptors is dynamically altered during binge and withdrawal. Furthermore, the expression of markers of excitatory postsynaptic signaling—PSD95; Homer-1 and -2 and the activity-regulated spine-morphing proteins Arc, LIM Kinase 1 and FOXP1—increase at late withdrawal. Notably, subchronic cannabidiol, during withdrawal, attenuates social- and novelty-induced aversion and passive stress-coping and rectifies the hyper-responsive stress axis and NAc dopamine and glutamate-related neuroplasticity. Overall, the exposure to binge-like alcohol levels in adolescent rats makes the NAc, during withdrawal, a locus minoris resistentiae as a result of perturbations in neuroplasticity and in stress-axis homeostasis. Cannabidiol holds a promising potential for increasing behavioural, neuroendocrine and molecular resilience against binge-like alcohol harmful effects. MDPI 2021-09-04 /pmc/articles/PMC8470908/ /pubmed/34572345 http://dx.doi.org/10.3390/biomedicines9091161 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Brancato, Anna Castelli, Valentina Lavanco, Gianluca Tringali, Giuseppe Micale, Vincenzo Kuchar, Martin D’Amico, Cesare Pizzolanti, Giuseppe Feo, Salvatore Cannizzaro, Carla Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return |
title | Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return |
title_full | Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return |
title_fullStr | Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return |
title_full_unstemmed | Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return |
title_short | Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return |
title_sort | binge-like alcohol exposure in adolescence: behavioural, neuroendocrine and molecular evidence of abnormal neuroplasticity… and return |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470908/ https://www.ncbi.nlm.nih.gov/pubmed/34572345 http://dx.doi.org/10.3390/biomedicines9091161 |
work_keys_str_mv | AT brancatoanna bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT castellivalentina bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT lavancogianluca bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT tringaligiuseppe bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT micalevincenzo bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT kucharmartin bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT damicocesare bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT pizzolantigiuseppe bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT feosalvatore bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn AT cannizzarocarla bingelikealcoholexposureinadolescencebehaviouralneuroendocrineandmolecularevidenceofabnormalneuroplasticityandreturn |