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Review ArticleReview Article

The Psychopharmacology of Effort-Related Decision Making: Dopamine, Adenosine, and Insights into the Neurochemistry of Motivation

John D. Salamone, Mercè Correa, Sarah Ferrigno, Jen-Hau Yang, Renee A. Rotolo and Rose E. Presby
Robert Dantzer, ASSOCIATE EDITOR
Pharmacological Reviews October 2018, 70 (4) 747-762; DOI: https://doi.org/10.1124/pr.117.015107
John D. Salamone
Department of Psychological Sciences, University of Connecticut, Storrs, Connecticut (J.D.S., S.F., J.-H.Y., R.A.R., R.E.P.); and Area de Psicobiologia, Universitat de Jaume I, Castelló, Spain (M.C.)
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Mercè Correa
Department of Psychological Sciences, University of Connecticut, Storrs, Connecticut (J.D.S., S.F., J.-H.Y., R.A.R., R.E.P.); and Area de Psicobiologia, Universitat de Jaume I, Castelló, Spain (M.C.)
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Sarah Ferrigno
Department of Psychological Sciences, University of Connecticut, Storrs, Connecticut (J.D.S., S.F., J.-H.Y., R.A.R., R.E.P.); and Area de Psicobiologia, Universitat de Jaume I, Castelló, Spain (M.C.)
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Jen-Hau Yang
Department of Psychological Sciences, University of Connecticut, Storrs, Connecticut (J.D.S., S.F., J.-H.Y., R.A.R., R.E.P.); and Area de Psicobiologia, Universitat de Jaume I, Castelló, Spain (M.C.)
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Renee A. Rotolo
Department of Psychological Sciences, University of Connecticut, Storrs, Connecticut (J.D.S., S.F., J.-H.Y., R.A.R., R.E.P.); and Area de Psicobiologia, Universitat de Jaume I, Castelló, Spain (M.C.)
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Rose E. Presby
Department of Psychological Sciences, University of Connecticut, Storrs, Connecticut (J.D.S., S.F., J.-H.Y., R.A.R., R.E.P.); and Area de Psicobiologia, Universitat de Jaume I, Castelló, Spain (M.C.)
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Robert Dantzer
Roles: ASSOCIATE EDITOR
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Abstract

Effort-based decision making is studied using tasks that offer choices between high-effort options leading to more highly valued reinforcers versus low-effort/low-reward options. These tasks have been used to study the involvement of neural systems, including mesolimbic dopamine and related circuits, in effort-related aspects of motivation. Moreover, such tasks are useful as animal models of some of the motivational symptoms that are seen in people with depression, schizophrenia, Parkinson’s disease, and other disorders. The present review will discuss the pharmacology of effort-related decision making and will focus on the use of these tasks for the development of drug treatments for motivational dysfunction. Research has identified pharmacological conditions that can alter effort-based choice and serve as models for depression-related symptoms (e.g., the vesicular monoamine transport-2 inhibitor tetrabenazine and proinflammatory cytokines). Furthermore, tests of effort-based choice have identified compounds that are particularly useful for stimulating high-effort work output and reversing the deficits induced by tetrabenazine and cytokines. These studies indicate that drugs that act by facilitating dopamine transmission, as well as adenosine A2A antagonists, are relatively effective at reversing effort-related impairments. Studies of effort-based choice may lead to the identification of drug targets that could be useful for treating motivational treatments that are resistant to commonly used antidepressants such as serotonin transport inhibitors.

Footnotes

  • Much of the work described in this review was supported by grants to J.D.S. from the National Institutes of Health National Institute of Mental Health, the UCONN Research Foundation, and Shire and Prexa, and to M.C. from MEC (PSI2015-68497-R).

  • https://doi.org/10.1124/pr.117.015107.

  • Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 70 (4)
Pharmacological Reviews
Vol. 70, Issue 4
1 Oct 2018
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Review ArticleReview Article

Pharmacology of Effort-Related Aspects of Motivation

John D. Salamone, Mercè Correa, Sarah Ferrigno, Jen-Hau Yang, Renee A. Rotolo and Rose E. Presby
Pharmacological Reviews October 1, 2018, 70 (4) 747-762; DOI: https://doi.org/10.1124/pr.117.015107

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Review ArticleReview Article

Pharmacology of Effort-Related Aspects of Motivation

John D. Salamone, Mercè Correa, Sarah Ferrigno, Jen-Hau Yang, Renee A. Rotolo and Rose E. Presby
Pharmacological Reviews October 1, 2018, 70 (4) 747-762; DOI: https://doi.org/10.1124/pr.117.015107
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  • Article
    • Abstract
    • I. Introduction: Motivational Processes and Psychopharmacology
    • II. Neural Circuits and Transmitters Mediating Effort-Based Choice: Mesolimbic Dopamine
    • III. Behavioral Effects of Dopaminergic Manipulations on Effort-Related Tasks Are Not Due to Broad or General Changes in Reward, Temporal Processing, or Motor Incapacity
    • IV. What Fundamental Processes Underlie the Low-Effort Bias Induced by Interference with Dopamine Transmission?
    • V. Neural Circuits and Transmitters Mediating Effort-Based Choice: Adenosine, GABA, and Nondopaminergic Components of the Circuit
    • VI. Clinical Implications: Targeting Drugs for the Potential Treatment of Effort-Based Dysfunctions
    • VII. Conclusions
    • Authorship Contributions
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    • Abbreviations
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