The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the catecholamine uptake blocker bupropion

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• 作者：Samantha E. Yohn ; Christian Thompson ; Patrick A. Randall…
• 关键词：Dopamine ; Accumbens ; Behavioral activation ; Motivation ; Reward ; Depression ; Fatigue ; Anergia
• 刊名：Psychopharmacology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：232
• 期：7
• 页码：1313-1323
• 全文大小：433 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Psychiatry
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-2072

文摘

Rationale Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine. Objectives The current studies investigated the effects of tetrabenazine on effort-based decision making using the T-maze barrier task. Methods Rats were tested in a T-maze in which the choice arms of the maze contain different reinforcement densities, and under some conditions, a vertical barrier was placed in the high-density arm to provide an effort-related challenge. The first experiment assessed the effects of tetrabenazine under different maze conditions: a barrier in the arm with 4 food pellets and 2 pellets in the no barrier arm (4- barrier), 4 pellets in one arm and 2 pellets in the other with no barrier in either arm (no barrier), and 4 pellets in the barrier arm with no pellets in the other (4- barrier). Results Tetrabenazine (0.25-.75?mg/kg IP) decreased selection of the high cost/high reward arm when the barrier was present, but had no effect on choice under the no barrier and 4- barrier conditions. The effects of tetrabenazine on barrier climbing in the 4- condition were reversed by the adenosine A2A antagonist MSX-3 and the catecholamine uptake inhibitor and antidepressant bupropion. Conclusions These studies have implications for the development of animal models of the motivational symptoms of depression and other disorders.