A role for the rs3796863 polymorphism in alcohol and monetary reward: evidence from CD38 knockout mice and alcohol self-administration, [11C]-raclopride binding, and functional MRI in humans.

: Cluster of differentiation 38 (CD38) is a transmembrane protein expressed in dopaminergic reward pathways in the brain, including the nucleus accumbens (NAc). The GG genotype of a common single nucleotide polymorphism (SNP) within , rs3796863, is associated with increased social reward.: Examine whether rs3796863 and knockout (KO) are associated with reward-related neural and behavioral phenotypes.: Data from four independent human studies were used to test whether rs3796863 genotype is associated with: (1) intravenous alcohol self-administration (n = 64, 30 females), (2) alcohol-stimulated dopamine (DA) release measured using C-raclopride positron emission tomography (n = 22 men), (3) ventral striatum (VS) response to positive feedback measured using a card guessing functional magnetic resonance imaging (fMRI) paradigm (n = 531, 276 females), and (4) resting state functional connectivity (rsfc) of the VS (n = 51, 26 females). In a fifth study, we used a mouse model to examine whether knockout influences stimulated DA release in the NAc core and dorsal striatum using fast-scanning cyclic voltammetry.: Relative to T allele carriers, G homozygotes at rs3796863 within were characterized by greater alcohol self-administration, alcohol-stimulated dopamine release, VS response to positive feedback, and rsfc between the VS and anterior cingulate cortex. High-frequency stimulation reduced DA release among KO mice had reduced dopamine release in the NAc.: Converging evidence suggests that rs3796863 genotype may increase DA-related reward response and alcohol consumption.