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

Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Psychopharmacology (Impact Factor: 3.88). 03/2010; 213(2-3):499-507. DOI: 10.1007/s00213-010-1798-7
Source: PubMed


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-HT(6) 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-HT(6) receptor agonists WAY-208466 and WAY-181187 using established behavioral tests in rats.
In order to determine if the 5-HT(6) 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-HT(6) receptor agonists were similar to those seen after treatment with the SSRI fluoxetine. Both 5-HT(6) 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-HT(6) 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.

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Available from: Irwin Lucki, Sep 23, 2014
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