title: Dopamine D₂ receptor modulation of human response inhibition and error awareness.
abstract: Response inhibition, comprising action cancellation and action restraint, and error awareness are executive functions of considerable clinical relevance to neuropsychiatric disorders. Nevertheless, our understanding of their underlying catecholamine mechanisms, particularly regarding dopamine, is limited. Here, we used the dopamine D2 agonist cabergoline to study its ability to improve inhibitory control and modulate awareness of performance errors. A randomized, double-blind, placebo-controlled, crossover design with a single dose of cabergoline (1.25 mg) and placebo (dextrose) was employed in 25 healthy participants. They each performed the stop-signal task, a well-validated measure of action cancellation, and the Error Awareness Task, a go/no-go measure of action restraint and error awareness, under each drug condition. Cabergoline was able to selectively reduce stop-signal RT, compared with placebo, indicative of enhanced action cancellation (p < .05). This enhancement occurred without concomitant changes in overall response speed or RT variability and was not seen for errors of commission on the Error Awareness Task. Awareness of performance errors on the go/no-go task was, however, significantly improved by cabergoline compared with placebo (p < .05). Our results contribute to growing evidence for the dopaminergic control of distinct aspects of human executive ability, namely, action cancellation and error awareness. The findings may aid the development of new, or the repurposing of existing, pharmacotherapy that targets the cognitive dysfunction of psychiatric and neurological disorders. They also provide further evidence that specific cognitive paradigms have correspondingly specific neurochemical bases.
authors.affiliation: The University of Queensland, Queensland, Australia. Lawrence_nandam@health.qld.gov.au
authors.forename: L Sanjay
authors.initials: LS
authors.lastname: Nandam
authors.forename: Robert
authors.initials: R
authors.lastname: Hester
authors.forename: Joe
authors.initials: J
authors.lastname: Wagner
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Dean
authors.forename: Cassandra
authors.initials: C
authors.lastname: Messer
authors.forename: Asha
authors.initials: A
authors.lastname: Honeysett
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bellgrove
mesh_terms: D000293:Adolescent; D000328:Adult; D001364:Awareness / Q000187:drug effects; D000077465:Cabergoline; D018491:Dopamine Agonists / Q000494:pharmacology; D004311:Double-Blind Method; D004873:Ergolines / Q000494:pharmacology; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D011930:Reaction Time / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017603:Signal Detection, Psychological / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D000077465:Cabergoline