Heritability of addictions is 40–60%, much of which is caused by genetic variations that affect underlying neurobiological mechanisms, and thus is consistent with there being common pathways to different addictions.152 Genes have been identified that convey vulnerability at all three stages of the addiction cycle, and salient candidates are discussed within this conceptual framework. However, a more comprehensive analysis is beyond the scope of this Review. In the binge/intoxication stage, several genes have been identified in animals as key to drug responses, and their modifications strongly affect drug self-administration.37,153–155 Notably, in animal models, dopamine D1 receptor knockout rats will not self-administer cocaine37 and μ opioid receptor knockout mice will not show the rewarding effects of opioids.153 In humans, only a few specific genes have been identified with polymorphisms (alleles) that either predispose an individual to or protect an individual from drug addiction,156 but the number is growing. For example, genome-wide association studies have implicated two acetylcholine receptors, the α4 nicotinic receptor subunit157 and α5 nicotinic receptor subunit,158 in the vulnerability to nicotine dependence and a single-nucleotide polymorphism associated with regulating the trafficking and gating properties of AMPA-selective glutamate receptors (CNIH3) in opioid dependence.159
