title: Mice lacking the melanin-concentrating hormone receptor-1 exhibit an atypical psychomotor susceptibility to cocaine and no conditioned cocaine response.
abstract: The present study aimed at characterizing the acute and intermittent psychomotor responsiveness to cocaine in mice lacking the MCHR1 receptor, which is thought to modulate the mesocorticolimbic sytem functioning [Smith DG, Tzavara ET, Shaw J, Luecke S, Wade M, Davis R, et al. Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor deficient mice. J Neurosci 2005;25:914-22]. On a first free-drug session, MCHR1-deficient mice exhibited significantly higher levels of locomotor activity elicited by the novelty of the test chambers than their wild-type counterparts. On the following day session, a first injection of 6 or 12 mg/kg cocaine induced comparable dose-related psychomotor activations in both genotypes, without significant difference in the relative increase in locomotion. Over the following eight once-daily test sessions, the slight psychomotor increase induced by 6 mg/kg was equivalent in both genotypes and constant over the sessions. At 12 mg/kg, cocaine induced a clear-cut incremental responsiveness to cocaine in both genotypes on the three first sessions; on the following sessions, only the wild-types displayed an incremental responsiveness until the last session, a sensitized effect that was confirmed for the wild-types but not for the knockouts on a subsequent sensitization test (cocaine challenge). Finally, the knockouts did not exhibit any sign of cocaine-conditioning (saline challenge), contrarily to the wild-types. It is speculated that MCHR1 may contribute to the neurobiological mechanisms of conditioned cocaine-induced psychomotor effects, possibly to those underpinning sensitization, and to a lesser extent to those sub-serving acute pharmacological cocaine action.
authors.affiliation: Unité de Recherche en Psychologie Expérimentale et Neurosciences Cognitives, Université de Liège, Boulevard du Rectorat, 5/B-32, Belgium.
authors.forename: Amélie
authors.initials: A
authors.lastname: Tyhon
authors.forename: Antoine
authors.initials: A
authors.lastname: Adamantidis
authors.forename: Agnès
authors.initials: A
authors.lastname: Foidart
authors.forename: Thierry
authors.initials: T
authors.lastname: Grisar
authors.forename: Bernard
authors.initials: B
authors.lastname: Lakaye
authors.forename: Ezio
authors.initials: E
authors.lastname: Tirelli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018765:Dopamine Uptake Inhibitors; C491209:Mchr1 protein, mouse; D017481:Receptors, Somatostatin; D003042:Cocaine