title: Modulation of inhibition of return by the dopamine D2 receptor agonist bromocriptine depends on individual DAT1 genotype.
abstract: 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.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA. arokem@gmail.com
authors.forename: Ariel
authors.initials: A
authors.lastname: Rokem
authors.forename: Ayelet N
authors.initials: AN
authors.lastname: Landau
authors.forename: William
authors.initials: W
authors.lastname: Prinzmetal
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Wallace
authors.forename: Michael A
authors.initials: MA
authors.lastname: Silver
authors.forename: Mark
authors.initials: M
authors.lastname: D'Esposito
mesh_terms: D001288:Attention / Q000187:drug effects / Q000502:physiology; D001971:Bromocriptine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics*; D011930:Reaction Time / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D001971:Bromocriptine; D004298:Dopamine