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

Rationale Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associatedwith working memory (WM) processing. The Tallele 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 spatialWMtask (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-BackWMtask. 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.