Genetics of dopamine receptors and drug addiction: a comprehensive review

Abstract

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.