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Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents.

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Title: Antidepressant-like effects of the novel, selective, 5-HT2C 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.
Source: Psychopharmacology. Jun2007, Vol. 192 Issue 2, p159-170. 12p. 2 Charts, 5 Graphs.
Subjects: Antidepressants, Mental depression, Aggression (Psychology), Animal models in research, Rats
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. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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