Effect of prenatal stress on alcohol preference and sensitivity to chronic alcohol exposure in male rats
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In rats, prenatal restraint stress (PRS) induces persistent behavioral and neurobiological alterations leading to a greater consumption of psychostimulants during adulthood. However, little is known about alcohol vulnerability in this animal model.
We examined in adolescent and adult male Sprague Dawley rats the long-lasting impact of PRS exposure on alcohol consumption.
PRS rats were subjected to a prenatal stress (three daily 45-min sessions of restraint stress to the mothers during the last 10 days of pregnancy). Alcohol preference was assessed in a two-bottle choice paradigm (alcohol 2.5%, 5%, or 10% versus water), in both naïve adolescent rats and adult rats previously exposed to a chronic alcohol treatment. Behavioral indices associated with incentive motivation for alcohol were investigated. Finally, plasma levels of transaminases (marker of hepatic damages) and ΔFosB levels in the nucleus accumbens (a potential molecular switch for addiction) were evaluated following the chronic alcohol exposure.
Alcohol preference was not affected by PRS. Contrary to our expectations, stressed and unstressed rats did not display signs of compulsive alcohol consumption. The consequences of the alcohol exposure on locomotor reactivity and on transaminase levels were more prominent in PRS group. Similarly, PRS potentiated alcohol-induced ΔFosB levels in the nucleus accumbens.
Our data suggest that negative events occurring in utero do not modulate alcohol preference in male rats but potentiate chronic alcohol-induced molecular neuroadaptation in the brain reward circuitry. Further studies are needed to determine whether the exacerbated ΔFosB upregulation in PRS rats could be extended to other reinforcing stimuli.
KeywordsMaternal restraint stress Ethanol Locomotor reactivity to novelty Gene regulation AST/ALT Corticosterone
This research was supported by the “Mission Interministérielle de Lutte contre les Drogues et les Toxicomanies” and the “Institut National de la Santé et de la Recherche Médicale” (MILDT-INSERM), the “Institut de Recherches Scientifiques sur les Boissons” (IREB), the “Pôle Interdisciplinaire de Recherche sur les Conduites Addictives” (PIRCAD), and the University of Lille 1. Vincent VAN WAES was funded by the “Conseil Régional du Nord–Pas de Calais.” Mihaela ENACHE was funded by the “Fonds Européens de Développement Régional.” We are grateful to Dr. Julien JACQUES for his statistical advice and to Giovanna BERNAL for the English revision of the manuscript. We thank Daniel DESCHAMPS and Serge LEFEVRE for animal care.
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