title: Role of melanin-concentrating hormone in the nucleus accumbens shell in rats behaviourally sensitized to methamphetamine.
abstract: Melanin-concentrating hormone (MCH) is a neuropeptide and its receptor is extensively expressed throughout the brain. MCH has been suggested to regulate the rewarding and reinforcing effects of psychostimulants by potentiating the dopaminergic system within the midbrain. Moreover, MCH and its receptor can regulate ERK activity. The present study investigated the role of MCH in the nucleus accumbens (NAc) in rats behaviourally sensitized to methamphetamine (Meth). We found that the development of Meth-induced locomotor sensitization was attenuated by MCH infused into the NAc shell but not core. Moreover, the elevation of ERK phosphorylation in the NAc shell induced by Meth was inhibited by locally infused MCH. Infusion of the MCH receptor 1 (MCHR1) antagonist SNAP 94847 into the NAc shell but not core augmented the initiation of locomotor sensitization and amplitude of elevated phosphorylated ERK levels induced by Meth. The expression of Meth-induced locomotor sensitization and ERK alterations after 1 wk withdrawal were not affected by either MCH or SNAP 94847 infused into the NAc shell or core. These results indicate that MCH in the NAc shell plays a critical role in the development but not expression of Meth-induced locomotor sensitization in rats, which might be mediated by the ERK signalling pathway. Our study suggests that MCH might be a potential target for the treatment of Meth addiction.
authors: National Institute on Drug Dependence, Peking University, B38 Xue Yuan Road, Haidian, Beijing, China.
authors: Li-Li
authors: LL
authors: Sun
authors: Yan
authors: Y
authors: Zhang
authors: Jian-feng
authors: JF
authors: Liu
authors: Jun
authors: J
authors: Wang
authors: Wei-li
authors: WL
authors: Zhu
authors: Li-yan
authors: LY
authors: Zhao
authors: Yan-xue
authors: YX
authors: Xue
authors: Lin
authors: L
authors: Lu
authors: Jie
authors: J
authors: Shi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D007028:Hypothalamic Hormones / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008543:Melanins / Q000378:metabolism* / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010907:Pituitary Hormones / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000697:Central Nervous System Stimulants; D007028:Hypothalamic Hormones; D008543:Melanins; C519479:N-(3-(1-((4-(3,4-difluorophenoxy)phenyl)methyl)(4-piperidyl))-4-methylphenyl)-2-methylpropanamide; D010880:Piperidines; D010907:Pituitary Hormones; D008694:Methamphetamine; C019463:melanin-concentrating hormone