title: DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine.
abstract: BACKGROUND
  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.
authors.affiliation: Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, 70124, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gelao
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fazio
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Selvaggi
authors.forename: Annabella
authors.initials: A
authors.lastname: Di Giorgio
authors.forename: Paolo
authors.initials: P
authors.lastname: Taurisano
authors.forename: Tiziana
authors.initials: T
authors.lastname: Quarto
authors.forename: Raffaella
authors.initials: R
authors.lastname: Romano
authors.forename: Annamaria
authors.initials: A
authors.lastname: Porcelli
authors.forename: Marina
authors.initials: M
authors.lastname: Mancini
authors.forename: Rita
authors.initials: R
authors.lastname: Masellis
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ursini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Simeis
authors.forename: Grazia
authors.initials: G
authors.lastname: Caforio
authors.forename: Laura
authors.initials: L
authors.lastname: Ferranti
authors.forename: Luciana
authors.initials: L
authors.lastname: Lo Bianco
authors.forename: Antonio
authors.initials: A
authors.lastname: Rampino
authors.forename: Orlando
authors.initials: O
authors.lastname: Todarello
authors.forename: Teresa
authors.initials: T
authors.lastname: Popolizio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolino
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D001971:Bromocriptine / Q000494:pharmacology*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D013647:Task Performance and Analysis
chemical_list: C581293:DRD2 protein, human; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D010100:Oxygen