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Article

Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return

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Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties of Excellence “G. D’Alessandro”, University of Palermo, 90127 Palermo, Italy
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Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
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INSERM U1215, NeuroCentre Magendie, 330300 Bordeaux, France
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University of Bordeaux, 33300 Bordeaux, France
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Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
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Pharmacology Section, Department of Health Care Surveillance and Bioethics, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy
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Department of Chemistry of Natural Compounds, University of Chemistry and Technology, 166 28 Prague, Czech Republic
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Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128 Palermo, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: James A. Marrs
Biomedicines 2021, 9(9), 1161; https://doi.org/10.3390/biomedicines9091161
Received: 7 August 2021 / Revised: 29 August 2021 / Accepted: 30 August 2021 / Published: 4 September 2021
(This article belongs to the Section Molecular and Translational Medicine)
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. View Full-Text
Keywords: binge alcohol drinking; adolescence; nucleus accumbens; cannabidiol binge alcohol drinking; adolescence; nucleus accumbens; cannabidiol
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MDPI and ACS Style

Brancato, A.; Castelli, V.; Lavanco, G.; Tringali, G.; Micale, V.; Kuchar, M.; D’Amico, C.; Pizzolanti, G.; Feo, S.; Cannizzaro, C. Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return. Biomedicines 2021, 9, 1161. https://doi.org/10.3390/biomedicines9091161

AMA Style

Brancato A, Castelli V, Lavanco G, Tringali G, Micale V, Kuchar M, D’Amico C, Pizzolanti G, Feo S, Cannizzaro C. Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return. Biomedicines. 2021; 9(9):1161. https://doi.org/10.3390/biomedicines9091161

Chicago/Turabian Style

Brancato, Anna, Valentina Castelli, Gianluca Lavanco, Giuseppe Tringali, Vincenzo Micale, Martin Kuchar, Cesare D’Amico, Giuseppe Pizzolanti, Salvatore Feo, and Carla Cannizzaro. 2021. "Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return" Biomedicines 9, no. 9: 1161. https://doi.org/10.3390/biomedicines9091161

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