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 two3-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.
RCT Entities:
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 DRD2rs1076560 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.
Authors: Håkan Fischer; Lars Nyberg; Sari Karlsson; Per Karlsson; Yvonne Brehmer; Anna Rieckmann; Stuart W S MacDonald; Lars Farde; Lars Bäckman Journal: Biol Psychiatry Date: 2010-03-15 Impact factor: 13.382
Authors: Venkata S Mattay; Terry E Goldberg; Francesco Fera; Ahmad R Hariri; Alessandro Tessitore; Michael F Egan; Bhaskar Kolachana; Joseph H Callicott; Daniel R Weinberger Journal: Proc Natl Acad Sci U S A Date: 2003-04-25 Impact factor: 11.205
Authors: G Pergola; P Di Carlo; E D'Ambrosio; B Gelao; L Fazio; M Papalino; A Monda; G Scozia; B Pietrangelo; M Attrotto; J A Apud; Q Chen; V S Mattay; A Rampino; G Caforio; D R Weinberger; G Blasi; A Bertolino Journal: Transl Psychiatry Date: 2017-01-17 Impact factor: 6.222