Psychopharmacology

, Volume 195, Issue 2, pp 223–234

Opposing effects of 5-HT2A and 5-HT2C receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test

  • Paul J. Fletcher
  • Maria Tampakeras
  • Judy Sinyard
  • Guy A. Higgins
Original Investigation

DOI: 10.1007/s00213-007-0891-z

Cite this article as:
Fletcher, P.J., Tampakeras, M., Sinyard, J. et al. Psychopharmacology (2007) 195: 223. doi:10.1007/s00213-007-0891-z

Abstract

Rationale

Serotonin (5-HT) has been linked to impulsivity with recent data suggesting that different receptor sub-types exert opposing influences on this behaviour.

Objectives

This work characterised the effects of 5-HT2A (ketanserin, (±)2,3-dimethoxyphenyl-1-[2–4-(piperidine)-methanol] [M100907]), 5-HT2B (6-chloro-5-methyl-1-(5-quinolylcarbamoyl) indoline [SB215505]) and 5-HT2C (6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbomyl] indoline [SB242084]) receptor antagonists on impulsive behaviour, measured in the five-choice serial reaction time test (5CSRTT), in rats and mice. The effects of (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) and (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 (Ro60-0175), two compounds that have been used extensively as agonists for the 5-HT2A and 5-HT2C receptor, were also measured.

Materials and methods

Rats and mice were trained on the 5CSRTT in which reinforcement is earned for detecting and correctly responding to brief presentations of a stimulus light. Impulsivity in this task is measured as premature responding, before stimulus presentation. Several variants of the task were used in which the inter-trial interval (ITI) length was manipulated to alter basal levels of premature responding.

Results

In the rat, ketanserin and M100907 reduced and SB242084 enhanced premature responding. SB215505 had no effect. DOI generally disrupted responding, while Ro60-0175 reduced premature responding when a long ITI was used. In mice, M100907 reduced and SB242084 increased premature responding when the ITI was lengthened. The effects of these drugs on other aspects of performance were less robust. M100907 and ketanserin did not affect response accuracy but tended to slow speed of responding; SB242084 occasionally increased speed of responding and slightly reduced accuracy.

Conclusions

Serotonin exerts both excitatory and inhibitory influences on motor impulsivity via 5-HT2A and 5-HT2C receptors in both rats and mice.

Keywords

Impulsivity 5-HT2A receptor 5-HT2C receptor M100907 SB242084 Five-choice serial reaction time test Rat Mouse Serotonin 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Paul J. Fletcher
    • 1
    • 2
    • 3
  • Maria Tampakeras
    • 1
  • Judy Sinyard
    • 1
  • Guy A. Higgins
    • 4
  1. 1.Section of BiopsychologyCentre for Addiction and Mental HealthTorontoCanada
  2. 2.Department of PsychiatryUniversity of TorontoTorontoCanada
  3. 3.Department of PsychologyUniversity of TorontoTorontoCanada
  4. 4.NPS PharmaceuticalsTorontoCanada

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