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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1448170

Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood

Provisionally accepted
Carles Colom-Rocha Carles Colom-Rocha Cristian Bis-Humbert Cristian Bis-Humbert M. Julia Garcia-Fuster M. Julia Garcia-Fuster *
  • University of the Balearic Islands, Palma de Mallorca, Spain

The final, formatted version of the article will be published soon.

    Background Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e., cannabidiol or ketamine) to prevent the observed effects.We performed 3 independent studies with male and female Sprague-Dawley rats, treated in adolescence (postnatal days, PND 29-38) with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Later on, adult rats were (1) scored for their affectivelike state (forced-swim, elevated-plus maze, novelty-suppressed feeding, sucrose preference),(2) allowed to freely drink ethanol for 6 weeks (two-bottle choice), or (3) treated with cannabidiol or ketamine before given access to ethanol in adulthood. Results No signs of increased negative affect were observed in adulthood following the adolescent treatments. However, adolescent ethanol exposure was a risk-factor for later developing an increased voluntary ethanol consumption in adulthood, both for male and female rats. This risk was similar when ethanol was combined with adolescent cocaine exposure, since cocaine alone showed no effects on later ethanol intake. Finally, rats exposed to adolescent ethanol and pretreated in adulthood with cannabidiol (and/or ketamine, but just for females) reduced their ethanol voluntary consumption. Conclusions Our data provided two therapeutical options capable of preventing the impact of an early drug initiation during adolescence by decreasing voluntary ethanol consumption in adult rats.• Adolescent ethanol exposure is a risk-factor for later voluntary ethanol consumption.• This increased vulnerability is observed both for male and female rats.• Adding cocaine exposure in adolescence does not increase the observed risk.• Cannabidiol (and/or ketamine, but just for females) reduced the observed risk.

    Keywords: Addiction risk factors, adolescence, alcohol use disorder, sex differences, Therapeutical options, rodent models Colom-Rocha, Bis-Humbert and García-Fuster 4

    Received: 12 Jun 2024; Accepted: 15 Aug 2024.

    Copyright: © 2024 Colom-Rocha, Bis-Humbert and Garcia-Fuster. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: M. Julia Garcia-Fuster, University of the Balearic Islands, Palma de Mallorca, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.