| Abstract | RATIONALE: Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of SSRIs. OBJECTIVE: The present studies were conducted to evaluate the effects of the novel 5-HT2C receptor agonist WAY-163909 in animal models of antidepressant activity (forced swim test (FST), resident-intruder, olfactory bulbectomy (BULB)), in a schedule-induced polydipsia (SIP) model of obsessive-compulsive disorder and in a model for evaluating sexual dysfunction. RESULTS: WAY-163909 (10 mg/kg, i.p. or s.c.) decreased immobility time in Wistar-Kyoto rats in the FST, effects that were reversed by the 5-HT2C/2B receptor antagonist SB 206553. Moreover, in Sprague-Dawley rats, the profile of WAY-163909 (decreased immobility, increased swimming) in the FST was comparable to the effects of SSRIs. Acute treatment with WAY-163909 (0.33 mg/kg, s.c.) decreased rodent aggression at doses lower than those required for decreasing total behavior. Administration of WAY-163909 (3 mg/kg, i.p.) for 5 or 21 days decreased the BULB-induced hyperactivity in rats. Additionally, acute administration of WAY-163909 (3 mg/kg, i.p.) decreased adjunctive drinking in a SIP model. The effects of WAY-163909 were reversed by the 5-HT(2C/2B) receptor antagonist SB 206553 and the selective 5-HT2C receptor antagonist SB 242084. Chronic administration of WAY-163909 produced deficits in sexual function at doses higher (10 mg/kg, i.p.) than those required for antidepressant-like effects in the BULB model. CONCLUSIONS: Taken together, these results demonstrate that the novel 5-HT2C receptor agonist WAY-163909 produces rapid onset antidepressant-like effects in animal models and may be a novel treatment for depression. |
| Authors | Sharon Rosenzweig-Lipson, Annmarie Sabb, Gary Stack, Paul Mitchell, Irwin Lucki, Jessica E Malberg, Steve Grauer, Julie Brennan, John F Cryan, Stacey J Sukoff Rizzo, John Dunlop, James E Barrett, Karen L Marquis
(Affiliation: Discovery Neuroscience, Wyeth Research, CN-8000, Princeton, NJ 08543, USA. rosenzs at wyeth.com)
|
| Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 192
Issue 2
Pg. 159-70
(Jun 2007)
ISSN: 0033-3158 Germany |
| PMID | 17297636
(Publication Type: Comparative Study, Journal Article)
|
| Chemical References |
- 1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta(b)(1,4)diazepino(6,7,1hj)indole
- Antidepressive Agents
- Azepines
- Indoles
- Receptor, Serotonin, 5-HT2C
- Serotonin Agonists
|
| Topics |
- Aggression
(drug effects)
- Animals
- Antidepressive Agents
(administration & dosage, adverse effects, pharmacology)
- Azepines
(administration & dosage, adverse effects, pharmacology)
- Depression
(drug therapy)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drinking Behavior
(drug effects)
- Female
- Indoles
(administration & dosage, adverse effects, pharmacology)
- Male
- Obsessive-Compulsive Disorder
(chemically induced, drug therapy)
- Rats
- Rats, Inbred WKY
- Rats, Long-Evans
- Rats, Sprague-Dawley
- Rats, Wistar
- Receptor, Serotonin, 5-HT2C
(drug effects, metabolism)
- Serotonin Agonists
(administration & dosage, adverse effects, pharmacology)
- Sexual Behavior, Animal
(drug effects)
- Sexual Dysfunction, Physiological
(chemically induced)
- Swimming
|
