title: Netrin G1: its downregulation in the nucleus accumbens of cocaine-conditioned mice and genetic association in human cocaine dependence.
abstract: Netrin G1 is a presynaptic ligand involved in axonal projection. Although molecular mechanisms underlying cocaine addiction are still poorly understood, Netrin G1 might have a role as a regulator of anxiety, fear and spatial memory, behavioural traits impaired in the context of cocaine exposure. In this study, the Netrin G1 (Ntng1) expression was investigated in the nucleus accumbens of mice primarily conditioned to cocaine using a place preference paradigm. A genetic association study was then conducted on 146 multiplex families of the Collaborative study on Genetics of Alcoholism, in which seven single nucleotide polymorphisms located in the NTNG1 gene were genotyped. NTNG1 expression levels were also quantified in BA10, BA46 and the cerebellum of healthy controls (with no Axis 1 psychopathology). Decreased Ntng1 expression was initially observed in the nucleus accumbens of mice conditioned to cocaine. Significant genetic family-based associations were detected between NTNG1 polymorphisms and cocaine dependence. NTNG1 expression in BA10, BA46 and the cerebellum, however, were not significantly associated with any allele or haplotype of this gene. These results confirm that Ntng1 expression is disturbed in the nucleus accumbens of mice, after cocaine conditioning. A haplotype of NTNG1 was found to constitute a vulnerability factor for cocaine use disorder in patients, although none of its single nucleotide polymorphisms were associated with a differential expression pattern in healthy controls. The data suggest that change in the Ntng1 expression is a consequence of cocaine exposure, and that some of its genetic markers are associated with a greater risk for cocaine use disorder.
authors.affiliation: INSERM U894, Centre de Psychiatrie & Neurosciences, University Paris Descartes, Paris, France.
authors.forename: Sabah
authors.initials: S
authors.lastname: Kelaï
authors.affiliation: INSERM U894, Centre de Psychiatrie & Neurosciences, University Paris Descartes, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ramoz
authors.affiliation: INSERM U894, Centre de Psychiatrie & Neurosciences, University Paris Descartes, Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Moalic
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche, France.|Institut national de la santé et de la recherche médicale, Paris, France.|Université Paris Descartes, Laboratoire de Neuropsychopharmacologie des Addictions, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Noble
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Canada.
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.affiliation: Centre de Génétique Moléculaire, FRE 3144, CNRS and Gif/Orsay DNA Microarray Platform (GODMAP), France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Imbeaud
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: INSERM U894, Centre de Psychiatrie & Neurosciences, University Paris Descartes, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Simonneau
authors.affiliation: INSERM U894, Centre de Psychiatrie & Neurosciences, University Paris Descartes, Paris, France.|Hôpital Sainte-Anne (CMME), University Paris Descartes, France.
authors.forename: Philip
authors.initials: P
authors.lastname: Gorwood
authors.affiliation: INSERM U894, Centre de Psychiatrie & Neurosciences, University Paris Descartes, Paris, France.|McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Maussion
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002531:Cerebellum / Q000378:metabolism; D003042:Cocaine; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000378:metabolism; D003213:Conditioning, Psychological; D018765:Dopamine Uptake Inhibitors; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D000075385:Netrins / Q000235:genetics* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D058851:GPI-Linked Proteins; C463082:NTNG1 protein, human; D000075385:Netrins; C000618035:Ntng1 protein, mouse; D012333:RNA, Messenger; D003042:Cocaine
keywords: SNP; addiction; cocaine; gene expression; mice; post-mortem brain