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

Journal Article (Journal Article)

Background : 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 CD38 , rs3796863, is associated with increased social reward.Objective : Examine whether CD38 rs3796863 and Cd38 knockout (KO) are associated with reward-related neural and behavioral phenotypes.Methods : 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 11 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 cd38 knockout influences stimulated DA release in the NAc core and dorsal striatum using fast-scanning cyclic voltammetry.Results : Relative to T allele carriers, G homozygotes at rs3796863 within CD38 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 Cd38 KO mice had reduced dopamine release in the NAc.Conclusion : Converging evidence suggests that CD38 rs3796863 genotype may increase DA-related reward response and alcohol consumption.

Full Text

Duke Authors

Cited Authors

  • Lee, MR; Shin, JH; Deschaine, S; Daurio, AM; Stangl, BL; Yan, J; Ramchandani, VA; Schwandt, ML; Grodin, EN; Momenan, R; Corral-Frias, NS; Hariri, AR; Bogdan, R; Alvarez, VA; Leggio, L

Published Date

  • January 2020

Published In

Volume / Issue

  • 46 / 2

Start / End Page

  • 167 - 179

PubMed ID

  • 31365285

Electronic International Standard Serial Number (EISSN)

  • 1097-9891

International Standard Serial Number (ISSN)

  • 0095-2990

Digital Object Identifier (DOI)

  • 10.1080/00952990.2019.1638928

Language

  • eng