NrCAM in addiction vulnerability: Positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice

Hiroki Ishiguro, Qing Rong Liu, Jian Ping Gong, Frank Scott Hall, Hiroshi Ujike, Marisela Morales, Takeshi Sakurai, Martin Grumet, George R. Uhl

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)572-584
Number of pages13
JournalNeuropsychopharmacology
Volume31
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Addiction
  • Association
  • Gene regulation
  • Morphine
  • Neuronal adhesion

ASJC Scopus subject areas

  • Pharmacology

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