title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 (4-2 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 (4-0 barrier).
  
  
  RESULTS
  Tetrabenazine (0.25-0.75 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 4-0 barrier conditions. The effects of tetrabenazine on barrier climbing in the 4-2 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.
authors.affiliation: Division of Behavioral Neuroscience, Department of Psychology, University of Connecticut, Storrs, CT, 06269-1020, USA.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Yohn
authors.forename: Christian
authors.initials: C
authors.lastname: Thompson
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Randall
authors.forename: Christie A
authors.initials: CA
authors.lastname: Lee
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Younis
authors.initials: Y
authors.lastname: Baqi
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology*; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D003657:Decision Making / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000502:physiology; D013747:Tetrabenazine / Q000494:pharmacology*; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D000928:Antidepressive Agents; D002395:Catecholamines; D018492:Dopamine Antagonists; C113602:MSX 3 compound; D043705:Receptor, Adenosine A2A; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D014970:Xanthines; D016642:Bupropion; D013747:Tetrabenazine