Marina Mori1, Iku Tsutsui-Kimura2,3,4, Masaru Mimura1, Kenji F Tanaka5. 1. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, 160-8582, Japan. 2. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, 160-8582, Japan. ikimura@fas.harvard.edu. 3. Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA. ikimura@fas.harvard.edu. 4. JSPS Overseas Research Fellow, Tokyo, 102-0083, Japan. ikimura@fas.harvard.edu. 5. Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, 160-8582, Japan. kftanaka@keio.jp.
Abstract
RATIONALE: Impulsive choice has often been evaluated in rodents according to the proportion of choices for the delayed large magnitude reinforcer (%large choice) in a delay-discounting task (DDT). However, because %large choice is influenced by both sensitivity to reinforcer magnitude and sensitivity to delayed reinforcement (i.e., discounting rate), distinctively evaluating such discounting parameters represents a critical issue demanding methods to determine each parameter in rats. The serotonin (5-HT) system is well known to be involved in impulsive choice; nevertheless, only a few studies have distinguished discounting parameters and investigated how 5-HT modulators affect discounting rate. OBJECTIVE: Here, we performed a discounting parameter analysis in mice and examined the effects of various 5-HT modulators on discounting rate. METHODS: We set up DDTs with different delay schedules to determine which schedule could address delay-discounting rates in mice. We examined the effect of the following drugs on impulsive choice: a 5-HT reuptake inhibitor (paroxetine), a 5-HT1A receptor agonist (8-OH-DPAT), and two 5-HT3 receptor antagonists (granisetron and ondansetron). RESULTS: Mice showed typical delay discounting at the shorter delay schedules (up to 4 s delay). The %large choice under shorter, but not longer, schedules followed an exponential function and allowed us to derive discounting rates. We selected a DDT with a 4-s delay schedule for further experiments. Granisetron and ondansetron, but not paroxetine or 8-OH-DPAT, decreased discounting rates without affecting sensitivity to reinforcer magnitude. CONCLUSION: We found that a method to calculate discounting rates in rats is also applicable to mouse models. We also provided evidence that 5-HT3 antagonism controls impulsive choice in mice.
RATIONALE: Impulsive choice has often been evaluated in rodents according to the proportion of choices for the delayed large magnitude reinforcer (%large choice) in a delay-discounting task (DDT). However, because %large choice is influenced by both sensitivity to reinforcer magnitude and sensitivity to delayed reinforcement (i.e., discounting rate), distinctively evaluating such discounting parameters represents a critical issue demanding methods to determine each parameter in rats. The serotonin (5-HT) system is well known to be involved in impulsive choice; nevertheless, only a few studies have distinguished discounting parameters and investigated how 5-HT modulators affect discounting rate. OBJECTIVE: Here, we performed a discounting parameter analysis in mice and examined the effects of various 5-HT modulators on discounting rate. METHODS: We set up DDTs with different delay schedules to determine which schedule could address delay-discounting rates in mice. We examined the effect of the following drugs on impulsive choice: a 5-HT reuptake inhibitor (paroxetine), a 5-HT1A receptor agonist (8-OH-DPAT), and two 5-HT3 receptor antagonists (granisetron and ondansetron). RESULTS:Mice showed typical delay discounting at the shorter delay schedules (up to 4 s delay). The %large choice under shorter, but not longer, schedules followed an exponential function and allowed us to derive discounting rates. We selected a DDT with a 4-s delay schedule for further experiments. Granisetron and ondansetron, but not paroxetine or 8-OH-DPAT, decreased discounting rates without affecting sensitivity to reinforcer magnitude. CONCLUSION: We found that a method to calculate discounting rates in rats is also applicable to mouse models. We also provided evidence that 5-HT3 antagonism controls impulsive choice in mice.
Authors: S Mobini; S Body; M-Y Ho; C M Bradshaw; E Szabadi; J F W Deakin; I M Anderson Journal: Psychopharmacology (Berl) Date: 2002-01-25 Impact factor: 4.530
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