, Volume 192, Issue 2, pp 159–170 | Cite as

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

  • 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
Original Investigation



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.


Forced swim test Resident–intruder Olfactory bulbectomy Schedule-induced polydipsia 5-HT2C receptor agonist WAY-163909 Antidepressant Rapid onset 



serotonin reuptake inhibitor


olfactory bulbectomy




forced swim test




analysis of variance


standard error of the mean


differential reinforcement of low rate


least significant difference


obsessive–compulsive disorder


schedule-induced polydipsia







The authors would like to thank Menelas Pangalos and Ron Magolda for their unwavering support of 5-HT2C agonist studies.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sharon Rosenzweig-Lipson
    • 1
  • Annmarie Sabb
    • 2
  • Gary Stack
    • 2
  • Paul Mitchell
    • 3
  • Irwin Lucki
    • 4
  • Jessica E. Malberg
    • 1
  • Steve Grauer
    • 1
  • Julie Brennan
    • 1
  • John F. Cryan
    • 4
  • Stacey J. Sukoff Rizzo
    • 1
  • John Dunlop
    • 1
  • James E. Barrett
    • 1
  • Karen L. Marquis
    • 1
  1. 1.Discovery NeuroscienceWyeth ResearchPrincetonUSA
  2. 2.Chemical and Screening SciencesWyeth ResearchPrincetonUSA
  3. 3.Department of Pharmacy and PharmacologyUniversity of BathBathUK
  4. 4.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA

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