Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence

Anatomical, pharmacological and human post-mortem studies suggest the dopamine D 3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Ball I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zuckerman scale) than controls (P=0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P= 0.038) or controls (P= 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Ball polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).