NrCAM in addiction vulnerability: positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice.
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.
Ishiguro
Hiroki
H
Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD 21224, USA.
Liu
Qing-Rong
QR
Gong
Jian-Ping
JP
Hall
Frank Scott
FS
Ujike
Hiroshi
H
Morales
Marisela
M
Sakurai
Takeshi
T
Grumet
Martin
M
Uhl
George R
GR
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
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D009294:Narcotics; C491151:Nrcam protein, mouse; D012333:RNA, Messenger; D009020:Morphine; D003042:Cocaine