부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.bbr.2006.06.007 Byline: Amelie Tyhon (b), Antoine Adamantidis (a), Agnes Foidart (a), Thierry Grisar (a), Bernard Lakaye (a), Ezio Tirelli (b) Keywords: MCHR1 receptor; Cocaine; Psychomotor activation; Sensitization; Novelty; Knockout mice; Conditioned drug 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 12mg/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 6mg/kg was equivalent in both genotypes and constant over the sessions. At 12mg/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. Author Affiliation: (a) Centre de Recherche en Neurobiologie Cellulaire et Moleculaire, Universite de Liege, Avenue de l'HA[acute accent]pital, 1/B-36, Belgium (b) Unite de Recherche en Psychologie Experimentale et Neurosciences Cognitives, Universite de Liege, Boulevard du Rectorat, 5/B-32, Belgium Article History: Received 3 February 2006; Revised 1 June 2006; Accepted 6 June 2006