DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine

Barbara Gelao, Leonardo Fazio, Pierluigi Selvaggi, Annabella Di Giorgio, Paolo Taurisano, Tiziana Quarto, Raffaella Romano, Annamaria Porcelli, Marina Mancini, Rita Masellis, Gianluca Ursini, Giuseppe De Simeis, Grazia Caforio, Laura Ferranti, Luciana Lo Bianco, Antonio Rampino, Orlando Todarello, Teresa Popolizio, Giuseppe Blasi, Alessandro Bertolino

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. Objective: We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). Methods: Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2- and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p<0.05, family-wise error corrected) was used. Results: On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. Conclusions: These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.

Original languageEnglish (US)
Pages (from-to)2361-2370
Number of pages10
JournalPsychopharmacology
Volume231
Issue number11
DOIs
StatePublished - Jun 2014

Keywords

  • Bromocriptine
  • DRD2 rs1076560
  • Dopamine
  • Prefrontal cortex
  • Working memory
  • fMRI

ASJC Scopus subject areas

  • Pharmacology

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