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

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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.

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Acknowledgments

We would like to acknowledge Riccarda Lomuscio BA; Apostolos Papazacharias MD, Ph.D.; Linda Antonucci Ph.D.; Caterina De Virgilio Ph.D.; Maria Teresa Attrotto MD; Federico La Torre Ph.D.; and Francesco D'Ascanio Ph.D. for their help with data acquisition. We also would like to express our thanks to all the volunteers for having participated to the study.

Conflict of interest

Dr. Bertolino is a full time employee of Hoffman-La Roche, Ltd. All other authors report no potential conflicts of interest.

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Authors and Affiliations

  1. Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Bari, 70124, Italy

    Barbara Gelao, Leonardo Fazio, Pierluigi Selvaggi, Paolo Taurisano, Tiziana Quarto, Raffaella Romano, Annamaria Porcelli, Marina Mancini, Rita Masellis, Gianluca Ursini, Luciana Lo Bianco, Antonio Rampino & Alessandro Bertolino

  2. IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo, Foggia, 71013, Italy

    Annabella Di Giorgio & Teresa Popolizio

  3. Cognitive Brain Research Unit, Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland

    Tiziana Quarto

  4. Department of Mental Health, ASL, Lecce, 73100, Italy

    Giuseppe De Simeis

  5. Azienda Ospedaliero-Universitaria Consorziale Policlinico, Bari, 70124, Italy

    Grazia Caforio & Giuseppe Blasi

  6. Psychiatric, Clinical Psychology and Psychiatric Rehabilitation Unit, Department of General and Experimental Medicine, University of Study of Perugia, Perugia, 06100, Italy

    Laura Ferranti

  7. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Bari, 70124, Italy

    Orlando Todarello

  8. Dipartimento di Scienze Mediche di Base, Neuroscienze ed Organi di Senso, Università degli Studi di Bari “Aldo Moro”, Piazza Giulio Cesare 11, Bari, 70124, Italy

    Alessandro Bertolino

  9. pRED, NORD DTA, F. Hoffman-La Roche Ltd., Basel, 4070, Switzerland

    Alessandro Bertolino

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  1. Barbara Gelao
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  2. Leonardo Fazio
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  3. Pierluigi Selvaggi
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  4. Annabella Di Giorgio
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  6. Tiziana Quarto
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  7. Raffaella Romano
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  8. Annamaria Porcelli
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  9. Marina Mancini
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  10. Rita Masellis
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  11. Gianluca Ursini
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  12. Giuseppe De Simeis
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  13. Grazia Caforio
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  14. Laura Ferranti
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  15. Luciana Lo Bianco
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  16. Antonio Rampino
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  17. Orlando Todarello
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  18. Teresa Popolizio
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  19. Giuseppe Blasi
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  20. Alessandro Bertolino
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Correspondence to Alessandro Bertolino.

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Gelao, B., Fazio, L., Selvaggi, P. et al. DRD2 genotype predicts prefrontal activity during working memory after stimulation of D2 receptors with bromocriptine. Psychopharmacology 231, 2361–2370 (2014). https://doi.org/10.1007/s00213-013-3398-9

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  • DOI: https://doi.org/10.1007/s00213-013-3398-9

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