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.
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Authors | Denis Boulay, Ronan Depoortere, Caroline Louis, Martine Lacave, Marie Thérèse Lucas, Guy Griebel |
Journal | Pharmacology, biochemistry, and behavior
(Pharmacol Biochem Behav)
Vol. 97
Issue 3
Pg. 428-35
(Jan 2011)
ISSN: 1873-5177 [Electronic] United States |
PMID | 20920519
(Publication Type: Journal Article)
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Copyright | Copyright © 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
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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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