The Antidepressant-Like Actions of Furosemide, Bumetanide and Nifedipine in the Forced Swim Test in Mice

Abstract

The effects on down-stream signalling and neuroplasticity are the ways the actions of the presently-used antidepressants, the tricarboxylic acids (TCAs) and the selective serotonin reuptake inhibitors (SSRIs) are enhanced and effected. The present study aims to determine whether the actions of the calcium channel blocker, nifedipine, and the loop diuretics, furosemide and bumetanide are enhanced on chronic administration in the forced swim (FST) model of depression in mice. Six groups (six mice in each group) of male albino mice (25-40g) were used. They were housed in a soundproof laboratory and allowed food and water ad libitum in labeled metal cages. Respective groups were pretreated with 5mg/kg of nifedipine, 10mg/kg of imipramine, 5mg/kg of sertraline, 2.5mg/kg of bumetanide and 10mg/kg of furosemide daily intra-peritoneally for 30 days. A control group received 0.25ml of placebo daily for 30 days. On the test days (Day 1, 15 and 31), the doses were gicen but those on furosemide received 100mg/ kg and the bumetanide group received 75mg/kg intra-peritoneally. Experiment using the forced swim test was then used to evaluate their effect on the prolongation of onset of the period of immobility in mice.The compounds enhanced the prolongation of period of onset of immobility over the acute treatment significantly (F(5,30)= 20.35; (p<0.01) and post-hoc DMR test showed imipramine produced the most significant response with bumetanide producing the least response. The order of magnitude of response was imipramine>sertraline>nifedipine> furosemide>bumetanide.

Keywords: FST, imipramine, sertraline, nifedipine, furosemide, bumetanide, chronic.