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Increase in water-depth increases the sensitivity of the forced swim test (FST) and it was deemed necessary to investigate the antidepressant-like activities of furosemide, bumetanide and nifedipine vis-à-vis the currently used antidepressants, imipramine and sertraline at different water-depths. Groups of mice with six mice each were divided into two batches of 10 groups for the experiments at the different water-depths of 15 and 30 cm in labelled plastic cages for (a) two control groups for treatment with 0.25 ml of 10% Tween 80; (b) two furosemide groups for treatment with 100 mg/kg of furosemide; (c) two bumetanide groups for treatment with 75 mg/kg of bumetanide; (d) two nifedipine groups for treatment with 5 mg/kg of nifedipine; (e) two imipramine groups for treatment with 10 mg/kg of imipramine; (f) two sertraline groups for treatment with 5 mg/kg of sertraline. Injections were administered intraperitoneally (i.p). 60 min elapsed before the test of immobility was carried out at the different water depths of 15 and 30 cm. The drug combinations furosemide + nifedipine, furosemide + imipramine and furosemide + sertraline were also tested at the 15 and 30 cm water-depths and also compared to controls. The five agents and the drug combinations caused significant responses in the delay or prolongation of the period of immobility over control values and over values obtained at the 15 cm water-depth (P < 0.05; < 0.005). Post-hoc Student-Newman-Keuls (SNK) test showed that while imipramine produced the most significant response at the 15 cm water-depth, furosemide produced the most significant response at the 30 cm water-depth. In summary, the antidepressant-like response of furosemide is enhanced significantly by increase of water-depth above that of the other agents.   Key words: Furosemide, bumetanide, nifedipine, imipramine, sertraline, water-depth, antidepressant.