title: Repeated agouti related peptide (83-132) injections inhibit cocaine-induced locomotor sensitisation, but not via the nucleus accumbens.
abstract: Drug addiction is a chronic relapsing brain disease for which many of the underlying neuronal mechanisms are yet to be unravelled. There seems to be an interaction between the melanocortin system and drugs of abuse. For instance, infusion of the melanocortin MC4 receptor antagonist SHU9119 (Ac-Nle-cyclo(-Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2) into the nucleus accumbens results in conditioned place avoidance, reduces the amount of lever presses for cocaine and blocks development of cocaine-induced locomotor sensitisation. The aim of this study is to determine whether the induction of locomotor sensitisation to repeated cocaine is inhibited by the melanocortin MC4 receptor inverse agonist Agouti Related Peptide (AgRP83-132). Rats were sensitised to daily cocaine injections for 5 consecutive days and 30 min prior to every daily cocaine injection, rats received an intracerebroventricular (i.c.v.) or intra nucleus accumbens injection with AgRP(83-132) or saline, to determine whether we could inhibit cocaine-induced locomotor sensitisation. We show that i.c.v. injections of AgRP(83-132) inhibit cocaine-induced locomotor sensitisation. This effect is not regulated via the nucleus accumbens, since injecting the melanocortin receptor inverse agonist AgRP(83-132) directly into the nucleus accumbens was unable to inhibit the cocaine-induced locomotor sensitisation. This implicates that the nucleus accumbens is an unlikely site to inhibit the induction of locomotor sensitisation via the melanocortin MC4 receptor. This is in contrast to other studies that show an effect of the melanocortin MC4 receptor antagonist SHU9119 on locomotor sensitisation when injected into the nucleus accumbens.
authors.affiliation: Rudolf Magnus Institute, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: Edwin
authors.initials: E
authors.lastname: Alserda
authors.affiliation: Rudolf Magnus Institute, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: Roger A H
authors.initials: RAH
authors.lastname: Adan
authors.affiliation: Rudolf Magnus Institute, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. Electronic address: g.m.j.ramakers@umcutrecht.nl.
authors.forename: Geert M J
authors.initials: GMJ
authors.lastname: Ramakers
mesh_terms: D054369:Agouti-Related Protein / Q000737:chemistry*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D054314:Drug Inverse Agonism; D004435:Eating / Q000187:drug effects; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000378:metabolism; D013997:Time Factors
chemical_list: D054369:Agouti-Related Protein; D010446:Peptide Fragments; D044105:Receptor, Melanocortin, Type 4; D003042:Cocaine
keywords: AgRP; Cocaine; Locomotor sensitisation; Nucleus accumbens