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Excess dopamine D4 receptor (D4DR) Exon III seven repeat allele in opioid dependent subjects

Molecular Psychiatry

Both twin studies in humans and studies on the pharmacogenetics of opioid addiction in rodents point to a role for heritability as a contributing factor in the development of drug dependence. This study may be the first to show a significant link between a specific genetic polymorphism and opioid dependence in humans. A group of 141 opioid dependent subjects, addicted to heroin, were genotyped for the exon III repeat polymorphism in the dopamine D4 receptor. The long alleles were significantly over represented in the opioid dependent cohort. The long form of this highly unusual polymorphism (chiefly represented by the 7 repeat allele), which contains multiple 16 amino acid repeats, has been previously shown to be associated with Novelty Seeking, a human personality trait characterized by impulsive and sensation seeking behavior. A number of studies have also shown that Novelty Seeking is prominent in substance abusers. The conferred risk for substance abuse in the population group carrying the long forms of the allele is a modest 2.46 which suggests that additional genes may eventually be identified that also predispose to addictive behavior in humans. For further information, please contact the corresponding author, Dr. Richard P. Ebstein, at the Research Laboratory, S. Herzog Memorial Hospital, Jerusalem, Israel; Tel: +972-2-5316855; Fax: +972-2-5316855; e-mail:

M Kotler, H Cohen, R Segman, I Gritsenko, L Nemanov, B Lerer, I Kramer, M Zer-Zion, I Kletz, RP Ebstein Ben-Gurion University of the Negev, Hadassah-Hebrew University Medical Center, Jerusalem, S Herzog Memorial Hospital, Jerusalem, Emek Hospital, and CITA Institute, Tel-Aviv, Israel

These articles will be published in the May issue of Molecular Psychiatry, an independent peer-reviewed journal published by Stockton Press/Macmillan Press.

Editor: Julio Licinio, MD - editorial assistant: Rachel Lisman
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For information on the scientific aspects of the article please contact the authors or the scientist who wrote an independent commentary. Pre-prints of the articles can be obtained from Ms. Rachel Lisman:
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