Cognitive, Behavioral, and Systems NeuroscienceResearch PaperBrain regions associated with the reversal of cocaine conditioned place preference by environmental enrichment
Highlights
▶Exposure to EE during a 30-day period of abstinence prevents the expression of cocaine CPP. ▶Only SE conditioned mice show significant induction of Fos expression in several brain areas. ▶The effects of EE are associated with a general inhibition of brain circuitry involved in relapse. ▶Expression of Fos is not found in unconditioned and saline control mice.
Section snippets
Animals
Seventy-two adult male C57/BL6 mice (Elevage Janvier, France), 10–12 weeks old, experimentally naïve at the start of the study, were housed in a temperature- and humidity-controlled room and maintained on a 12 h light/dark cycle with the lights on from 7:00 am–7:00 pm and had ad libitum access to food and water. All experimentation was conducted during the light period. Experiments were carried out in accordance with the European Communities Council Directive of November 24, 1986 (86/609/EEC)
Cocaine seeking behavior in SE and EE mice
As previously shown (Solinas et al., 2008), after 30 days of withdrawal, conditioned SE mice showed significant preferences for the compartment previously associated with cocaine compared to saline-treated mice whereas the preference for cocaine-paired compartment was completely lost in conditioned EE mice (Fig. 3A). As expected, SE and EE saline as well as unconditioned groups showed no CPP. Statistical analysis demonstrated no significant main effect for environment or treatment but a
Discussion
In this study, we have found that the “curative” effects of EE on cocaine seeking behavior are associated with a general inhibition in the activation of the brain neurocircuitry involved in relapse, including cortical, motor, and limbic structures that have previously been shown to be involved in cocaine seeking behavior in rodents (Bossert et al., 2005, Kalivas, 2008, Koob and Le Moal, 2001). In fact, all the regions that were significantly activated in SE mice conditioned to cocaine compared
Acknowledgments
The authors thank N. Thiriet for helpful comments on the manuscript and A. Gaillard for advices on the immunohistochemistry procedures. This work was supported by Centre National de la Recherche Scientifique (CNRS), University of Poitiers, Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie, Région Poitou-Charentes, and the Contrat de Projet Etat Region (CPER) #5. C. Chauvet is a recipient of a PhD fellowship from the French Ministry of Research.
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