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Social stress under binge-like alcohol withdrawal in adolescence: evidence of cannabidiol effect on maladaptive plasticity in rats

Published online by Cambridge University Press:  06 September 2022

Anna Brancato*
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties ‘G. D’ Alessandro’, University of Palermo, Palermo, Italy
Valentina Castelli
Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
Gianluca Lavanco
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties ‘G. D’ Alessandro’, University of Palermo, Palermo, Italy
Cesare D'Amico
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy
Salvatore Feo
Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy ATEN Center, Genomic and Proteomic Laboratory, University of Palermo, Palermo, Italy
Giuseppe Pizzolanti
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties ‘G. D’ Alessandro’, University of Palermo, Palermo, Italy
Martin Kuchar
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, 166 28 Prague, Czech Republic
Carla Cannizzaro
Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
Author for correspondence: Anna Brancato, E-mail:



Alcohol binge drinking may compromise the functioning of the nucleus accumbens (NAc), i.e. the neural hub for processing reward and aversive responses.


As socially stressful events pose particular challenges at developmental stages, this research applied the resident–intruder paradigm as a model of social stress, to highlight behavioural neuroendocrine and molecular maladaptive plasticity in rats at withdrawal from binge-like alcohol exposure in adolescence. In search of a rescue agent, cannabidiol (CBD) was selected due to its favourable effects on alcohol- and stress-related harms.


Binge-like alcohol exposed intruder rats displayed a compromised defensive behaviour against the resident and a blunted response of the stress system, in addition to indexes of abnormal dopamine (DA)/glutamate plasticity and dysfunctional spine dynamics in the NAc. CBD administration (60 mg/kg) was able to: (1) increase social exploration in the binge-like alcohol exposed intruder rats, at the expenses of freezing time, and in control rats, which received less aggressive attacks from the resident; (2) reduce corticosterone levels independently on alcohol previous exposure; (3) restore DA transmission and (4) facilitate excitatory postsynaptic strength and remodelling.


Overall, the maladaptive behavioural and synaptic plasticity promoted by the intersection between binge-like alcohol withdrawal and exposure to adverse social stress can be rescued by a CBD détente effect that results in a successful defensive strategy, supported by a functional endocrine and synaptic plasticity. The current data highlight CBD's relevant therapeutic potential in alcohol- and stress-related harms, and prompt further investigation on its molecular targets.

Original Article
Copyright © The Author(s), 2022. Published by Cambridge University Press

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