title: Human cognitive flexibility depends on dopamine D2 receptor signaling.
abstract: BACKGROUND
  Accumulating evidence indicates that the cognitive effects of dopamine depend on the subtype of dopamine receptor that is activated. In particular, recent work with animals as well as current theorizing has suggested that cognitive flexibility depends on dopamine D2 receptor signaling. However, there is no evidence for similar mechanisms in humans.
  
  
  OBJECTIVE
  We aim to demonstrate that optimal dopamine D2 receptor signaling is critical for human cognitive flexibility.
  
  
  METHODS
  To this end, a pharmacological pretreatment design was employed. This enabled us to investigate whether effects of the dopamine receptor agonist bromocriptine on task-set switching were abolished by pretreatment with the D2 receptor antagonist sulpiride. To account for individual (genetic) differences in baseline levels of dopamine, we made use of a common variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the dopamine transporter gene, DAT1.
  
  
  RESULTS
  Bromocriptine improved cognitive flexibility relative to placebo, but only in subjects with genetically determined low levels of dopamine (n = 27). This beneficial effect of bromocriptine on cognitive flexibility was blocked by pretreatment with the selective dopamine D2 receptor antagonist sulpiride (n = 14).
  
  
  CONCLUSIONS
  These results provide strong evidence in favor of the hypothesis that human cognitive flexibility implicates dopamine D2 receptor signaling.
authors: Donders Institute for Brain, Cognition and Behaviour (RU/DI-BCB), Radboud University Nijmegen, Kapittelweg 29, 6521 EN Nijmegen, the Netherlands. m.vanholstein@donders.ru.nl
authors: Mieke
authors: M
authors: van Holstein
authors: Esther
authors: E
authors: Aarts
authors: Marieke E
authors: ME
authors: van der Schaaf
authors: Dirk E M
authors: DE
authors: Geurts
authors: Robbert J
authors: RJ
authors: Verkes
authors: Barbara
authors: B
authors: Franke
authors: Martine R
authors: MR
authors: van Schouwenburg
authors: Roshan
authors: R
authors: Cools
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