The 5-HT3 receptor agonist attenuates the action of antidepressants in the forced swim test in rats.

Involvement of 5-hydroxytryptamine (5-HT)3 receptors in action of antidepressants was examined in the forced swim test in rats. Rats were forced to swim in a cylinder for 15 min on day 1 and for 5 min on day 2. Imipramine, desipramine and mianserin, administered after the 15-min swim session on day 1 and before the 5-min swim test on day 2, dose-dependently decreased the duration of immobility in the swim test on day 2. 1-(m-Chlorophenyl)-biguanide (mCPBG) attenuated the decreased duration of immobility induced by imipramine, desipramine and mianserin, although mCPBG did not affect the duration of immobility when it was given alone. ICS205-930 dose-dependently decreased the duration of immobility in the swim test on day 2, and the effect of ICS205-930 was attenuated by mCPBG. These results suggest that the suppression of 5-HT3 receptor activity may contribute to the action of antidepressants.