Antidepressant and anxiolytic effects of selective 5-HT6 receptor agonists in rats

Gregory V. Carr, Lee E. Schechter, Irwin Lucki

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: Although selective serotonin reuptake inhibitors (SSRIs) produce clinical therapeutic effects on depression and anxiety through augmentation of serotonergic neurotransmission, there is little known about the potential contributions of the 5-HT6 receptor in the treatment of mood disorders. Objectives: The aim of this study was to test the potential antidepressant-like and anxiolytic-like effects of the 5-HT6 receptor agonists WAY-208466 and WAY-181187 using established behavioral tests in rats. Methods: In order to determine if the 5-HT6 receptor agonists possess antidepressant-like activity, rats were treated with WAY-208466 or WAY-181187 and tested in the modified rat forced swim test (FST). Also, the potential anxiolytic-like effects of WAY-208466 and WAY-181187 were measured using the defensive burying (DB) test and novelty-induced hypophagia (NIH) test. Results: WAY-208466 and WAY-181187 produced both antidepressant-like and anxiolytic-like effects. Both compounds decreased immobility and increased swimming behavior in the FST. The effects of the 5-HT6 receptor agonists were similar to those seen after treatment with the SSRI fluoxetine. Both 5-HT6 receptor agonists also decreased burying duration in the DB test, indicative of anxiolytic activity in the test. The anxiolytic effects of WAY-208466 were reproduced in the NIH test. Assessment of the anxiolytic effects of WAY-181187 in the NIH was confounded by alterations in home cage feeding behavior. Conclusions: These findings suggest that 5-HT6 receptor agonists may represent a new class of potential antidepressant and anxiolytic compounds and could possess a number of advantages over currently available treatments, including rapid onset of anxiolytic efficacy.

Original languageEnglish (US)
Pages (from-to)499-507
Number of pages9
JournalPsychopharmacology
Volume213
Issue number2-3
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • 5-HT receptor
  • Antidepressants
  • Anxiety
  • Defensive burying
  • Depression
  • Forced swim test
  • Noveltyinduced hypophagia
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

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