Matthew R Bailey1,2, Cait Williamson3, Chris Mezias4, Vanessa Winiger5, Rae Silver3,4,6, Peter D Balsam4,7,5, Eleanor H Simpson8,9. 1. Department of Psychology, Columbia University, New York, NY, USA. mrb2225@columbia.edu. 2. Columbia University, Mail Code 5501, 1190 Amsterdam Avenue Room 406, Schermerhorn Hall, New York, NY, 10027, USA. mrb2225@columbia.edu. 3. Department of Psychology, Columbia University, New York, NY, USA. 4. Barnard College, Columbia University, New York, NY, USA. 5. New York State Psychiatric Institute, New York, NY, USA. 6. Department of Pathology and Cell Biology, Columbia University Health Sciences, New York, NY, USA. 7. Department of Psychiatry, Columbia University, 1051 Riverside Drive, Box 87, New York, NY, 10032, USA. 8. Department of Psychiatry, Columbia University, 1051 Riverside Drive, Box 87, New York, NY, 10032, USA. es534@columbia.edu. 9. New York State Psychiatric Institute, New York, NY, USA. es534@columbia.edu.
Abstract
RATIONALE: 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. OBJECTIVES: 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.
RATIONALE: 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. OBJECTIVES: 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.
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