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SSR181507, a dopamine D₂ receptor and 5-HT(₁A) receptor ligand: evidence for mixed anxiolytic- and antidepressant-like activities.

Abstract
SSR181507, a dopamine D₂ receptor antagonist/partial agonist and 5-HT(₁A) receptor agonist, is active in animal models of schizophrenia. Furthermore, it shows activity in several anxiety and/or depression models (Depoortere et al. 2003). Presently, we sought to further characterize the latter two activities in rats, using a step-down passive avoidance procedure, a shock-induced ultrasonic vocalization (UV) test in adult subjects and a social interaction test. SSR181507 (0.3 & 1 mg/kg ip), but not the atypical antipsychotics clozapine and olanzapine, decreased the latency time to step-down from a "safety" platform. Effects of SSR181507 were reversed by the selective 5-HT(₁A) receptor antagonist SL88.0338. SSR181507 also reduced UV (0.3 & 1 mg/kg ip), an effect not reversed by SL88.0338, and observed with olanzapine, haloperidol, fluoxetine and the 5-HT(₁A) receptor agonists 8-OH-DPAT and buspirone, but not diazepam. Furthermore, SSR181507 remained active following 3 weeks of administration (1 mg/kg ip, once daily) in the UV test. Lastly, SSR181507 (3 mg/kg ip) potentiated social interaction, an effect shared by diazepam and buspirone, but not by olanzapine, clozapine, haloperidol and 8-OH-DPAT. These data further strengthen previous findings that the putative atypical antipsychotic SSR181507 has mixed antidepressant and anxiolytic activities.
AuthorsDenis Boulay, Ronan Depoortere, Caroline Louis, Martine Lacave, Marie Thérèse Lucas, Guy Griebel
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 97 Issue 3 Pg. 428-35 (Jan 2011) ISSN: 1873-5177 [Electronic] United States
PMID20920519 (Publication Type: Journal Article)
CopyrightCopyright © 2010 Elsevier Inc. All rights reserved.
Chemical References
  • (3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine monohydrochloride
  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Dioxanes
  • Ligands
  • Receptors, Dopamine D2
  • Tropanes
  • Receptor, Serotonin, 5-HT1A
Topics
  • Animal Communication
  • Animals
  • Anti-Anxiety Agents (pharmacology)
  • Antidepressive Agents (pharmacology)
  • Behavior, Animal (drug effects)
  • Dioxanes (pharmacology)
  • Ligands
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A (drug effects, metabolism)
  • Receptors, Dopamine D2 (drug effects, metabolism)
  • Tropanes (pharmacology)

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