Neurotransmitter receptor gene expression patterns associated with reward-related neural representations

The neural representation of reward is underpinned by neurotransmitter systems; however, current human neuroimaging techniques cannot assess the receptor-specific contributions to reward processing. We investigated the relationships between reward-related neural representations and the expression patterns of 30 neurotransmitter receptor genes by combining meta-analytic functional neuroimaging maps with gene expression data from the Allen Human Brain Atlas. Clustering analysis revealed that serotonin receptor 2 A was co-expressed with other reward-related receptors, whereas the nociceptin (NOP) receptor exhibited a distinct expression pattern. Using elastic net regression with spatial null models, we observed that monetary reward maps showed significant positive spatial correlations with serotonin receptor 2 A expression and negative correlations with NOP receptor expression. Similar positive correlations with serotonin receptor 2 A were observed in the craving maps. Principal component regression provided complementary evidence, with both monetary reward and craving maps showing significant associations with components characterized by NOP receptor loadings. These findings from multiple analytical approaches suggest that reward processing involves both coordinated receptor networks and specialized receptor systems, particularly highlighting the opposing roles of the serotonin receptor 2 A and NOP systems. Our results provide insights into the molecular mechanisms underlying reward processing in the human brain, potentially informing targeted interventions for reward-related disorders.