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

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

In: Psychopharmacology, 2014, vol. 231, no. 11, p. 2361-2370

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    Title
    • DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine
    Author
    • Gelao, Barbara. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Fazio, Leonardo. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Selvaggi, Pierluigi. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Di Giorgio, Annabella. IRCCS "Casa Sollievo della Sofferenza”, 71013, San Giovanni Rotondo, Foggia, Italy
    • Taurisano, Paolo. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Quarto, Tiziana. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Romano, Raffaella. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Porcelli, Annamaria. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Mancini, Marina. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Masellis, Rita. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Ursini, Gianluca. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • De Simeis, Giuseppe. Department of Mental Health, ASL, 73100, Lecce, Italy
    • Caforio, Grazia. Azienda Ospedaliero-Universitaria Consorziale Policlinico, 70124, Bari, Italy
    • Ferranti, Laura. Psychiatric, Clinical Psychology and Psychiatric Rehabilitation Unit, Department of General and Experimental Medicine, University of Study of Perugia, 06100, Perugia, Italy
    • Lo Bianco, Luciana. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Rampino, Antonio. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Todarello, Orlando. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    • Popolizio, Teresa. IRCCS "Casa Sollievo della Sofferenza”, 71013, San Giovanni Rotondo, Foggia, Italy
    • Blasi, Giuseppe. Azienda Ospedaliero-Universitaria Consorziale Policlinico, 70124, Bari, Italy
    • Bertolino, Alessandro. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro”, 70124, Bari, Italy
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:325361
    Summary
    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.