title: NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice.
abstract: Several lines of evidence support roles for the cell adhesion molecule NrCAM in addictions. Fine mapping within a chromosome 7 region that contains previously linked and associated genomic markers identifies NrCAM haplotypes that are associated with substance abuse vulnerabilities in four samples of abusers and controls. Differential display identifies NrCAM as a drug regulated gene. NrCAM is expressed in neurons linked to reward and memory. NrCAM displays haplotype-specific gene expression in human post-mortem brain samples. Knockout mice display reduced opiate- and stimulant-conditioned place preferences. These observations support NrCAM as a positionally cloned and drug-regulated gene whose variants are likely to change expression and alter substance abuse vulnerabilities in human addictions and animal models of drug reward.
authors.affiliation: Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD 21224, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Liu
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Gong
authors.forename: Frank Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Marisela
authors.initials: M
authors.lastname: Morales
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Martin
authors.initials: M
authors.lastname: Grumet
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
mesh_terms: D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000523:psychology; D000818:Animals; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000523:psychology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D019966:Substance-Related Disorders / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D009294:Narcotics; C491151:Nrcam protein, mouse; D012333:RNA, Messenger; D009020:Morphine; D003042:Cocaine