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- Title
Antidepressant-like effects of the novel, selective, 5-HT<sub>2C</sub> receptor agonist WAY-163909 in rodents.
- Authors
Rosenzweig-Lipson, Sharon; Sabb, Annmarie; Stack, Gary; Mitchell, Paul; Lucki, Irwin; Malberg, Jessica E.; Grauer, Steve; Brennan, Julie; Cryan, John F.; Rizzo, Stacey J. Sukoff; Dunlop, John; Barrett, James E.; Marquis, Karen L.
- Abstract
Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of SSRIs. 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. 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-HT2C/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. 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.
- Subjects
ANTIDEPRESSANTS; MENTAL depression; AGGRESSION (Psychology); ANIMAL models in research; RATS
- Publication
Psychopharmacology, 2007, Vol 192, Issue 2, p159
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-007-0710-6