title: Antidepressant and anxiolytic effects of selective 5-HT6 receptor agonists in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Gregory V
authors.initials: GV
authors.lastname: Carr
authors.forename: Lee E
authors.initials: LE
authors.lastname: Schechter
authors.forename: Irwin
authors.initials: I
authors.lastname: Lucki
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013550:Swimming; D013844:Thiazoles / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D008744:Methylamines; C525454:N(1)-(6-chloroimidazo(2,1-b)(1,3)thiazole-5-sulfonyl)tryptamine; C558330:N-(2-(3-(3-fluorophenylsulfonyl)-1H-pyrrolo(2,3-b)pyridin-1-yl)ethyl)-N,N-dimethylamine; D011725:Pyridines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013844:Thiazoles; D014363:Tryptamines; C097216:serotonin 6 receptor