PT - JOURNAL ARTICLE AU - Cryan, John F. AU - Lucki, Irwin TI - Antidepressant-Like Behavioral Effects Mediated by 5-Hydroxytryptamine<sub>2C</sub> Receptors DP - 2000 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1120--1126 VI - 295 IP - 3 4099 - http://jpet.aspetjournals.org/content/295/3/1120.short 4100 - http://jpet.aspetjournals.org/content/295/3/1120.full SO - J Pharmacol Exp Ther2000 Dec 01; 295 AB - The role of the 5-HT2C receptor in mediating active behaviors in the modified rat forced swim test was examined. Three novel selective 5-HT2C receptor agonists, WAY 161503 (0.1–3.0 mg/kg), RO 60-0175 (2–20 mg/kg), and RO 60-0332 (20 mg/kg), all decreased immobility and increased swimming, a pattern of behavior similar to that which occurs with the selective serotonin reuptake inhibitor fluoxetine (5–20 mg/kg). However, the prototypical but nonselective 5-HT2C receptor agonistm-chlorophenylpiperazine (1–10 mg/kg) increased immobility scores in the forced swim test. The selective 5-HT2C receptor antagonist SB 206533 was inactive when given alone (1–20 mg/kg). However, SB 206533 (20 mg/kg) blocked the antidepressant-like effects of both WAY 161503 (1 mg/kg) and fluoxetine (20 mg/kg). The atypical antidepressant (noradrenergic α2and 5-HT2C receptor antagonist) mianserin reduced immobility and increased climbing at 30 mg/kg. At a behaviorally subactive dose (10 mg/kg), mianserin abolished the effects of WAY 161503 (1 mg/kg) on both swimming and immobility scores. Mianserin blocked the effects of fluoxetine (20 mg/kg) on swimming only; mianserin plus fluoxetine reduced immobility and induced a switch to climbing behavior, suggesting activation of noradrenergic transmission. These data exemplify the benefits of using the modified rat forced swim test, which was sensitive to serotonergic compounds and distinguished behavioral changes associated with serotonergic and noradrenergic effects. Taken together, the results strongly implicate a role for 5-HT2C receptors in the behavioral effects of antidepressant drugs. The American Society for Pharmacology and Experimental Therapeutics