The VMAT-2 Inhibitor Tetrabenazine Affects EffortRelated Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs
Scholar | Other documents of the author: Randall, Patrick A.; Lee, Christie A.; Nunes, Eric J.; Yohn, Samantha E.; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, Venkata Kiran; Makriyannis, Alexandros; Baqi, Younis; Müller, Christa E.; Correa Sanz, Mercè; Salamone, John D.
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TitleThe VMAT-2 Inhibitor Tetrabenazine Affects EffortRelated Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs
Publisher versionhttp://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.p ...
PublisherPublic Library of Science
Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major ... [+]
Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients. [-]
Bibliographic citationRandall PA, Lee CA, Nunes EJ, Yohn SE, Nowak V, Khan B, et al. (2014) The VMAT-2 Inhibitor Tetrabenazine Affects Effort-Related Decision Making in a Progressive Ratio/Chow Feeding Choice Task: Reversal with Antidepressant Drugs. PLoS ONE 9(6): e99320. doi:10.1371/journal.pone.0099320
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Except where otherwise noted, this item's license is described as © 2014 Randall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.