Repository logo
 

Effects of dopamine D2/D3 receptor antagonism on human planning and spatial working memory

Accepted version
Peer-reviewed

Change log

Authors

Naef, M 
Müller, U 
Linssen, A 
Clark, L 
Robbins, TW 

Abstract

Psychopharmacological studies in humans suggest important roles for dopamine (DA) D2 receptors in human executive functions, such as cognitive planning and spatial working memory (SWM). However, studies that investigate an impairment of such functions using the selective DA D2/3 receptor antagonist sulpiride have yielded inconsistent results, perhaps because relatively low doses were used. We believe we report for the first time, the effects of a higher (800 mg p.o.) single dose of sulpiride as well as of genetic variation in the DA receptor D2 gene (DA receptor D2 Taq1A polymorphism), on planning and working memory. With 78 healthy male volunteers, we apply a between-groups, placebo-controlled design. We measure outcomes in the difficult versions of the Cambridge Neuropsychological Test Automated Battery One-Touch Stockings of Cambridge and the self-ordered SWM task. Volunteers in the sulpiride group showed significant impairments in planning accuracy and, for the more difficult problems, in SWM. Sulpiride administration speeded response latencies in the planning task on the most difficult problems. Volunteers with at least one copy of the minor allele (A1+) of the DA receptor D2 Taq1A polymorphism showed better SWM capacity, regardless of whether they received sulpiride or placebo. There were no effects on blood pressure, heart rate or subjective sedation. In sum, a higher single dose of sulpiride impairs SWM and executive planning functions, in a manner independent of the DA receptor D2 Taq1A polymorphism.

Description

Keywords

Adult, Cognition, Dopamine Antagonists, Dopamine D2 Receptor Antagonists, Double-Blind Method, Humans, Male, Polymorphism, Genetic, Psychopharmacology, Reaction Time, Receptors, Dopamine D2, Receptors, Dopamine D3, Spatial Memory, Sulpiride

Journal Title

Translational Psychiatry

Conference Name

Journal ISSN

2158-3188
2158-3188

Volume Title

7

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (G0001354)
Medical Research Council (G1000183)
Wellcome Trust (104631/Z/14/Z)
Wellcome Trust (093875/Z/10/Z)
This research work was funded by a Core Award from the Medical Research Council and the Wellcome Trust to the Behavioural and Clinical Neuroscience Institute (MRC Ref G1000183; WT Ref 093875/Z/10/Z). Also supported by a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) awarded to TWR. CE was supported by the Swiss National Science Foundation (PA00P1_134135) and the Vienna Science and Technology Fund (WWTF VRG13-007).