title: Implication of CCR2 chemokine receptor in cocaine-induced sensitization.
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.
authors.affiliation: AP-HP, Department of Neurology, Lariboisiere Hospital, Paris, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Trocello
authors.forename: William
authors.initials: W
authors.lastname: Rostene
authors.forename: Stephane
authors.initials: S
authors.lastname: Melik-Parsadaniantz
authors.forename: David
authors.initials: D
authors.lastname: Godefroy
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roze
authors.forename: Patrick
authors.initials: P
authors.lastname: Kitabgi
authors.forename: William A
authors.initials: WA
authors.lastname: Kuziel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chalon
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Caboche
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Apartis
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine; D004298:Dopamine