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Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation

Molecular Psychiatry volume 18, pages 1025–1033 (2013)Cite this article

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Abstract

A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction and attention deficit hyperactivity disorder. As disruption of D2R signaling in the ventral striatum—including the nucleus accumbens (NAc)—impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that postsynaptic D2R overexpression in the NAc specifically increases an animal’s willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc.

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Acknowledgements

We thank Claudia Schmauss for the generous gift of D2R KO mice and Christoph Kellendonk for discussion and comments on the manuscript. This work was supported, in part, by US National Institutes of Health Grants DA022413, MH054137 (to JAJ), MH068073 (to PDB), MH068073 (to PDB), MH086404 (to JAJ, HM, EHS), by The Sidney R Baer Jr Foundation (to HM), by a Research Associate Award from the Research Foundation for Mental Hygiene (to PT), an EMBO Long-Term fellowship and the Basque Country Government (to EU), National Institute of Mental Health Grant F32MH090750-01 (to RDW) and by the Lieber Center for Schizophrenia Research and Treatment. PT, JAJ, EHS, PDB and HM designed research; PT, BF, EU and VW performed research; PT, RDW, KMT, PDB and HM analyzed the data; and PT, EHS, PDB, HM, DM and JAJ wrote the paper. All the authors participated in interpreting the data and edited the manuscript.

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Authors and Affiliations

  1. Department of Neuroscience, Columbia University, New York, NY, USA

    P Trifilieff, V Winiger & R D Ward

  2. New York State Psychiatric Institute, New York, NY, USA

    P Trifilieff, D Martinez, H Moore, P D Balsam, E H Simpson & J A Javitch

  3. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA

    B Feng, E Urizar, R D Ward, K M Taylor, D Martinez, H Moore, P D Balsam, E H Simpson & J A Javitch

  4. Department of Psychology, Barnard College, New York, NY, USA

    P D Balsam

  5. Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    J A Javitch

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  1. P Trifilieff
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Correspondence to J A Javitch.

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Trifilieff, P., Feng, B., Urizar, E. et al. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol Psychiatry 18, 1025–1033 (2013). https://doi.org/10.1038/mp.2013.57

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