BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1668957
Combining ethanol and cocaine exposure during adolescence increased cocaine reward sensitivity in adult rats as assessed by a single exposure place preference paradigm
Provisionally accepted- University of the Balearic Islands, Palma de Mallorca, Spain
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There is an urgent need for better understanding the long-term impact of polysubstance use initiation during adolescence. Our preclinical study examined the combined impact of ethanol and cocaine during a vulnerable window in adolescence on the long-term changes on cocaine reward emerging throughout withdrawal in adulthood. Male and female Sprague-Dawley rats were treated in adolescence with non-contingent paradigms of ethanol, cocaine, their combination or vehicle. Cocaine reward was assessed in adult rats, following prolonged withdrawal, by a simple paradigm based on a single exposure place preference previously characterized in mice, which was validated for Sprague-Dawley male and female adult rats.The main results demonstrated an increased impact of combining drugs (ethanol with cocaine) during adolescence on the outcome observed in adulthood, since a single exposure to cocaine increased the rewarding response induced by cocaine in these animals (i.e., increased time spent in the cocaine paired compartment). The combination of drugs during adolescence seemed to overcome that initial lack of response observed by just one of the drugs, thus presenting an augmented risk-factor for later consequences in adult rats of both sexes. To conclude, an early adolescent combined drug experience proved clear consequences on the emerging addictive-like behaviors observed in adulthood for both sexes.
Keywords: adolescence, polysubstance use, Vulnerability to cocaine addiction, Biological sex, Validating
Received: 18 Jul 2025; Accepted: 17 Aug 2025.
Copyright: © 2025 Colom-Rocha 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
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