title: Bupropion increases selection of high effort activity in rats tested on a progressive ratio/chow feeding choice procedure: implications for treatment of effort-related motivational symptoms.
abstract: BACKGROUND
  Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology.
  
  
  METHODS
  Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber.
  
  
  RESULTS
  Bupropion (10.0-40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation.
  
  
  CONCLUSIONS
  The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans.
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Randall
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Christie A
authors.initials: CA
authors.lastname: Lee
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Podurgiel
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Evan
authors.initials: E
authors.lastname: Hart
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Yohn
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Myles
authors.initials: M
authors.lastname: Jones
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Margaret
authors.initials: M
authors.lastname: Rowland
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Laura
authors.initials: L
authors.lastname: López-Cruz
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa).
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT (Drs Randall, Lee, Podurgiel, Hart, Yohn, Jones, Rowland, Correa, and Salamone); Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC (Dr Randall); Department of Chemistry, North Carolina State University, NC (Dr Lee); Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, Castelló, Spain (Drs López-Cruz and Correa). john.salamone@uconn.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
mesh_terms: D000818:Animals; D016642:Bupropion / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005502:Food; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule
chemical_list: D018765:Dopamine Uptake Inhibitors; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497930:Ppp1r1b protein, rat; D011619:Psychotropic Drugs; D016642:Bupropion; D004298:Dopamine
keywords: animal models; depression; dopamine; fatigue; nucleus accumbens