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.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Rogóz
Z
Z
Skuza
G
G
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004357:Drug Synergism; D005473:Fluoxetine / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
D000928:Antidepressive Agents; D005473:Fluoxetine; D008376:Maprotiline; C027299:hydroxymaprotilin; D016291:Dizocilpine Maleate; D011224:Prazosin