Human cognitive flexibility depends on dopamine D2 receptor signaling

✍ Scribed by Mieke van Holstein; Esther Aarts; Marieke E. van der Schaaf; Dirk E. M. Geurts; Robbert J. Verkes; Barbara Franke; Martine R. van Schouwenburg; Roshan Cools

• Publisher: Springer
• Year: 2011
• Tongue: English
• Weight: 467 KB
• Volume: 218
• Category: Article
• ISSN: 0033-3158
• DOI: 10.1007/s00213-011-2340-2

✦ Synopsis

Rationale

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.

Objectives

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.

Electronic supplementary material

The online version of this article (doi:10.1007/s00213-011-2340-2) contains supplementary material, which is available to authorized users.