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

• Published in: Psychopharmacology 2018-09, Vol.235 (9), p.2619-2629
• Main Authors: Mori, Marina, Tsutsui-Kimura, Iku, Mimura, Masaru, Tanaka, Kenji F.
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animal models; Biomedical and Life Sciences; Biomedicine; Delayed reinforcement; Exponential functions; Investigations; Laboratory animals; Mice; Neurosciences; Original Investigation; Paroxetine; Pharmacology/Toxicology; Psychiatry; Psychopharmacology; Rats; Reinforcement; Rodents; Schedules; Sensitivity; Serotonin; Serotonin S1 receptors; Serotonin S3 receptors
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-4954-0

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-HT 1A receptor agonist (8-OH-DPAT), and two 5-HT 3 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-HT 3 antagonism controls impulsive choice in mice.