5-HT4 receptors do not mediate the antidepressant-like behavioral effects of fluoxetine in a modified forced swim test

The receptors responsible for mediating the antidepressant effects of selec tive serotonin reuptake inhibitors are largely unknown. The role of the 5-H T4 receptor in mediating the antidepressant-like effects of fluoxetine in a modified rat forced swim test was examined. Fluoxetine (20 mg/kg) decrease d immobility and increased swimming, a pattern shown to represent its actio ns on the serotonergic system. The selective 5-HT4 receptor antagonist, SE 204070A [8-amino-7-chloro-(N-butyl-4-piperidyl)methylbenzo-1,4-dioxan-5-car boxylatehydrochloride] (0.1-3 mg/kg), failed to change any of the active be haviors in the test compared with saline-treated animals. Upon combination, SE 204070A (3 mg/kg) failed to alter the effects of fluoxetine effects in the test. These data therefore suggest that activation of postsynaptic 5-HT 4 receptors, subsequent to reuptake inhibition by fluoxetine, is not necess ary for its antidepressant-like behavioral effects in this test. (C) 2000 E lsevier Science B.V. All rights reserved.