The effects of combined treatment with MK-801 and antidepressant drugs in the forced swimming test in rats.

We found previously that combined administration of imipramine, citalopram and, to a lesser extent, mianserin with MK-801, a non-competitive NMDA receptor antagonist, reduced the immobility time in the forced swimming test in rats more potently than administration of the antidepressant or MK-801 alone. In present paper we examined the effect of other antidepressants in this model. (+)-Oxaprotiline and (-)-oxaprotiline which, when given alone, showed a weak positive effect, increased the action of MK-801. Fluoxetine, inactive when given alone, markedly increased the effect of MK-801. Moreover, the positive effect after combined treatment was found in the experiments in which antidepressants and MK-801 given separately were inactive. A reduction in the immobility time was also observed in those experimental paradigms in which the locomotor activity was not increased. The effects of combined treatment with the antidepressants studied + MK-801 were antagonized by haloperidol, but not by prazosin. The obtained results indicate that mainly a dopamine mechanism seems to be involved in the synergistic action of MK-801 and the antidepressants in the forced swimming test.