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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Adolescent, Adult, Bromocriptine, Cognition, Cross-Over Studies, Dopamine Agonists, Dopamine Antagonists, Dopamine Plasma Membrane Transport Proteins, Double-Blind Method, Female, Humans, Male, Polymorphism, Genetic, Receptors, Dopamine D2, Signal Transduction, Sulpiride, Tandem Repeat Sequences, Young Adult.
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Does human cognitive flexibility depend on dopamine D2 receptor signaling? Context: 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. We aim to demonstrate that optimal dopamine D2 receptor signaling is critical for human cognitive flexibility. 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. 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).
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These results provide strong evidence in favor of the hypothesis that human cognitive flexibility implicates dopamine D2 receptor signaling. Final Decision: yes