Drug dependence is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviours persist despite serious negative consequences. Addictive substances, such as opioids, ethanol, psychostimulants and nicotine, induce pleasant states or relieve distress, effects that contribute to their recreational use. Dopamine is critically involved in drug addiction processes. However, the role of the various dopaminergic receptor subtypes has been difficult to delineate. Here, we will review the information collected implicating the receptors of the D1 family (DRD1 and DRD5) and of the D2 family (DRD2, DRD3 and DRD4) in drug addiction. We will summarize the distribution of these receptors in the brain, the preclinical experiments carried out with pharmacological and transgenic approaches and the genetic studies carried out linking genetic variants of these receptors to drug addiction phenotypes. A meta-analysis of the studies carried out evaluating DRD2 and alcohol dependence is also provided, which indicates a significant association. Overall, this review indicates that different aspects of the addiction phenotype are critically influenced by dopaminergic receptors and that variants of those genes seem to influence some addiction phenotypes in humans.

Recent evidence has identified the NR4A1 (NUR77, NGFI-B) gene as a strong candidate for involvement in tardive dyskinesia (TD). We have investigated the association of six single nucleotide polymorphisms within the NR4A family of genes with TD in a sample of 171 patients with schizophrenia of Caucasian descent. The NR4A1 single nucleotide polymorphism (SNP) marker rs2603751 showed a nominal association with the risk of TD, as well as with the extent of TD based on the Abnormal Involuntary Movements Scale (AIMS) scores. The haplotype generated by the markers rs2603751 and rs2701124 also showed association with TD and, after adjustment for multiple testing, both the NR4A1 marker rs2603751 and the haplotype continued to show a trend toward association with TD. Although the results of this study are limited by a small sample size, it presents important pilot data and warrants further investigation of the involvement of NR4A1 variants in TD.

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