Dopamine, norepinephrine, and the management of sensorimotor bindings: individual differences in updating of stimulus–response episodes are predicted by DAT1, but not DBH5′-ins/del

Abstract

Evidence suggests that the flexibility of managing (creating and updating) stimulus-response bindings is driven by the dopaminergic system. Given that striatal dopamine (DA) plays a crucial role in the updating of working memory, the present study tested whether individual differences in the efficiency of updating stimulus-response episodes (event files) are predicted by differences in genetic predisposition related to the efficiency of the striatal dopaminergic pathway. In view of contrasting claims that stimulus-response binding is related to norepinephrine, we also considered genetic predispositions regarding noradrenergic pathways. In a sample of 100 healthy adults, we studied whether the degree to which stimulus-response bindings affect ongoing performance is predicted by polymorphisms of the dopamine transporter gene (DAT1, associated with striatal DA levels) and DBH5'-ins/del (strongly correlated with dopamine beta-hydroxylase, the enzyme catalyzing the dopamine-norepinephrine conversion). The performance of 9-repeat carriers of the DAT1 gene was more affected by stimulus-response bindings than the performance of 10/10 homozygotes was, while DBH5'-ins/del polymorphism was not related to performance. This outcome pattern suggests a crucial role of the nigrostriatal dopaminergic pathway in the flexible management of stimulus-response episodes, whereas norepinephrine does not seem to play a role.