Abstract
Cocaine-induced sensitization induces long-term neuroplastic changes in the striatum. Among these, extracellular signal-regulated kinase (ERK) is a fundamental component in striatal gene and epigenetic regulation and plays an important role in reward processes. As previous studies suggested that the chemokine CCL2 enhanced striatal dopamine release and as its cognate CCR2 receptor was located in brain structures implicated in cocaine reward, we tested the hypothesis that CCR2/CCL2 could be involved in cocaine-induced behavioral response. We used CCR2 knockout mice (CCR2−/−) and studied two crucial steps in cocaine sensitization: locomotor activity in sensitized mice and ERK activation in the striatum. We show that locomotor sensitization is significantly reduced in CCR2−/− mice as well as the dopamine transporter regulation and the cocaine-induced p-ERK striatal activation. Taken together, our results suggest that CCR2 receptor is involved in cocaine sensitization.
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Acknowledgment
This work was supported by Institut National de la Sante et de la Recherche Medicale (INSERM) and by grants from Fondation de France and Association France Parkinson. The authors would like to thank Pierre Casanova for his precious help in the animal facility, Patricia Mechighel and Lucette Gareau for their technical assistance.
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Trocello, J.M., Rostene, W., Melik-Parsadaniantz, S. et al. Implication of CCR2 Chemokine Receptor in Cocaine-Induced Sensitization. J Mol Neurosci 44, 147–151 (2011). https://doi.org/10.1007/s12031-011-9508-4
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DOI: https://doi.org/10.1007/s12031-011-9508-4