Humans vary substantially in their alcohol responses, and this variability is related to genetic susceptibility for alcohol use disorders, which accounts for more than half the disease risk in this condition 5,6. Striatal DA-release is a common element of drug reward 7, and alcohol-induced DA release has been shown both in rodents 8,9 and humans 10. There is, however, marked individual variation in alcohol-induced behavioral responses thought to be related to DA activation, such as psychomotor stimulation. Functional variation in opioid genes may contribute to this variation by modulating alcohol-induced DA release. A functional OPRM1 118G variant 11 confers enhanced subjective alcohol responses 12, and a functionally equivalent rhesus macaque 77G variant 13 confers enhanced alcohol-induced psychomotor stimulation 14. Despite this, it remains controversial whether the OPRM1 A118G polymorphism is a risk factor for alcohol use disorders 15.
