Polymorphisms in the Delta Opioid Receptor Gene (OPRD1) and Drug Addiction: Candidate Genes, Transgenic Mouse Models, and Genome-Wide Association Studies

The OPRD1 gene encodes delta opioid receptors (DORs). Opioids receptor agonists are involved in mediating reward. Numerous human candidate gene studies reported associations between various OPRD1 polymorphisms and addiction, including opioid, cocaine, and alcohol dependence. Transgenic mouse studies using knockout mice suggested that some OPRD1 variants might regulate drug reinforcement, emotional states, and behavioral inhibition. Individuals with OPRD1 risk variants may use drugs because of their specific personality features. At the same time, drug-induced changes in neurotransmitter systems may adversely affect personality traits, making some individuals even more likely to abuse drugs. Several OPRD1 polymorphisms are involved in the etiology of both Alzheimer's disease and addiction, and a number of other heritable brain-based phenotypes co-occur with drug abuse. DORs are involved in neuroprotection, and their expression is affected by several epigenetic factors. Both obese and drug-addicted individuals suffer from impairments in reward sensitivity, and opioids are involved in these processes.