title: The effects of pharmacological modulation of the serotonin 2C receptor on goal-directed behavior in mice.
abstract: BACKGROUND
  Impaired goal-directed motivation represents a debilitating class of symptoms common to psychological disorders including schizophrenia and some affective disorders. Despite the known negative impact of impaired motivation, there are currently no effective pharmacological interventions to treat these symptoms.
  
  
  OBJECTIVE
  Here, we evaluate the effectiveness of the serotonin 2C (5-HT2C) receptor selective ligand, SB242084, as a potential pharmacological intervention for enhancing goal-directed motivation in mice. The studies were designed to identify not only efficacy but also the specific motivational processes that were affected by the drug treatment.
  
  
  METHODS
  We tested subjects following treatment with SB242084 (0.75 mg/kg) in several operant lever pressing assays including the following: a progressive ratio (PR) schedule of reinforcement, an effort-based choice task, a progressive hold down task (PHD), and various food intake tests.
  
  
  RESULTS
  Acute SB242084 treatment leads to an increase in instrumental behavior. Using a battery of behavioral tasks, we demonstrate that the major effect of SB242084 is an increase in the amount of responses and duration of effort that subjects will make for food rewards. This enhancement of behavior is not the result of non-specific hyperactivity or arousal nor is it due to changes in food consumption.
  
  
  CONCLUSIONS
  Because of this specificity of action, we suggest that the 5-HT2C receptor warrants further attention as a novel therapeutic target for treating pathological impairments in goal-directed motivation.
authors.affiliation: Department of Psychology, Columbia University, New York, NY, USA. mrb2225@columbia.edu.|Columbia University, Mail Code 5501, 1190 Amsterdam Avenue Room 406, Schermerhorn Hall, New York, NY, 10027, USA. mrb2225@columbia.edu.
authors.forename: Matthew R
authors.identifier: http://orcid.org/0000-0002-9570-7505
authors.initials: MR
authors.lastname: Bailey
authors.affiliation: Department of Psychology, Columbia University, New York, NY, USA.
authors.forename: Cait
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Barnard College, Columbia University, New York, NY, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Mezias
authors.affiliation: New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Winiger
authors.affiliation: Department of Psychology, Columbia University, New York, NY, USA.|Barnard College, Columbia University, New York, NY, USA.|Department of Pathology and Cell Biology, Columbia University Health Sciences, New York, NY, USA.
authors.forename: Rae
authors.initials: R
authors.lastname: Silver
authors.affiliation: Barnard College, Columbia University, New York, NY, USA.|Department of Psychiatry, Columbia University, 1051 Riverside Drive, Box 87, New York, NY, 10032, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Balsam
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, Box 87, New York, NY, 10032, USA. es534@columbia.edu.|New York State Psychiatric Institute, New York, NY, USA. es534@columbia.edu.
authors.forename: Eleanor H
authors.initials: EH
authors.lastname: Simpson
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005260:Female; D006040:Goals; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D012201:Reward; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists
keywords: Feeding; Locomotor activity; Motivation; Operant; SB242084; Serotonin receptor