, Volume 213, Issue 2, pp 499–507

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

Original Investigation

DOI: 10.1007/s00213-010-1798-7

Cite this article as:
Carr, G.V., Schechter, L.E. & Lucki, I. Psychopharmacology (2011) 213: 499. doi:10.1007/s00213-010-1798-7



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.


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.


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.


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.


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.


SerotoninDepressionAnxiety5-HT6 receptorAntidepressantsForced swim testNovelty-induced hypophagiaDefensive burying

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Gregory V. Carr
    • 1
    • 2
  • Lee E. Schechter
    • 3
    • 4
  • Irwin Lucki
    • 1
    • 2
  1. 1.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of PharmacologyUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Wyeth ResearchPrincetonUSA
  4. 4.Pfizer, External R&D InnovationPrincetonUSA