Modulation of inhibition of return by the dopamine D2 receptor agonist bromocriptine depends on individual DAT1 genotype

Involuntary visual spatial attention is captured when a salient cue appears in the visual field. If a target appears soon after the cue, response times to targets at the cue location are faster relative to other locations. However, after longer cue-target intervals, responses to targets at the cue location are slower, due to inhibition of return (IOR). IOR depends on striatal dopamine (DA) levels: It varies with different alleles of the DA transporter gene DAT1 and is reduced in patients with Parkinson's disease, a disease characterized by reduced striatal dopaminergic transmission. We examined the role of DA in involuntary attention and IOR by administering the DA D2 receptor-specific agonist bromocriptine to healthy human subjects. There was no effect of either DAT1 genotype or bromocriptine on involuntary attention, but participants with DAT1 alleles predicting higher striatal DA had a larger IOR. Furthermore, bromocriptine increased the magnitude of IOR in participants with low striatal DA but abolished the IOR in subjects with high striatal DA. This inverted U-shaped pattern resembles previously described relationships between DA levels and performance on cognitive tasks and suggests an involvement of striatal DA in IOR that does not include a role in involuntary attention.