5-HT3 antagonists decrease discounting rate without affecting sensitivity to reward magnitude in the delay discounting task in mice

Marina Mori, Iku Tsutsui-Kimura, Masaru Mimura, Kenji Tanaka

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1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalPsychopharmacology
DOIs
Publication statusAccepted/In press - 2018 Jun 28

Fingerprint

Serotonin 5-HT3 Receptor Antagonists
Reward
Serotonin
Appointments and Schedules
Granisetron
8-Hydroxy-2-(di-n-propylamino)tetralin
Ondansetron
Paroxetine
Serotonin 5-HT1 Receptor Agonists
Receptors, Serotonin, 5-HT3
Receptor, Serotonin, 5-HT1A
DDT
Rodentia
Delay Discounting
Pharmaceutical Preparations

Keywords

  • Delay discounting task
  • Exponential function
  • Granisetron
  • Impulsive choice
  • Ondansetron
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "5-HT3 antagonists decrease discounting rate without affecting sensitivity to reward magnitude in the delay discounting task in mice",
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.",
keywords = "Delay discounting task, Exponential function, Granisetron, Impulsive choice, Ondansetron, Serotonin",
author = "Marina Mori and Iku Tsutsui-Kimura and Masaru Mimura and Kenji Tanaka",
year = "2018",
month = "6",
day = "28",
doi = "10.1007/s00213-018-4954-0",
language = "English",
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T1 - 5-HT3 antagonists decrease discounting rate without affecting sensitivity to reward magnitude in the delay discounting task in mice

AU - Mori, Marina

AU - Tsutsui-Kimura, Iku

AU - Mimura, Masaru

AU - Tanaka, Kenji

PY - 2018/6/28

Y1 - 2018/6/28

N2 - 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.

AB - 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.

KW - Delay discounting task

KW - Exponential function

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KW - Ondansetron

KW - Serotonin

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