1. ¹Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, MD, USA
2. ²Department of Neuropsychiatry, Okayama University Medical School, Okayama, Japan
3. ³Cellular Neuroscience Branch, NIDA-IRP, Baltimore, MD, USA
4. ⁴Department of Neurobiology, Mt Sinai School of Medicine, New York, NY, USA
5. ⁵Keck Ctr Collab. Neurosci, Rutgers University, Piscataway, NJ, USA

Correspondence: Dr GR Uhl, Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180, Baltimore, MD 21224, USA. Tel: +1 410 550 2843 ext. 146; Fax: +1 410 550 1535; E-mail: guhl@intra.nida.nih.gov

Received 24 February 2005; Revised 26 April 2005; Accepted 3 June 2005; Published online 10 August 2005.

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.