THE SYNERGISTIC EFFECT OF FLUOXETINE ON THE LOCOMOTOR HYPERACTIVITY INDUCED BY MK-801, A NONCOMPETITIVE NMDA RECEPTOR ANTAGONIST

It was found previously that the MK-801 (an uncompetitive NMDA recepto r antagonist)-induced locomotor hyperactivity in rats was potently inc reased by antidepressant drugs. The present paper analysed the locomot or hyperactivity induced by combined treatment with fluoxetine + MK-80 1 in male Wistar rats. The MK-801 hyperactivity was increased by cital opram (the latter effect was prevented by zacopride and ketanserin), s ertraline, p-chloramphetamine, 8-OH-DPAT and TFMPP. The hyperlocomotio n caused by fluoxetine + MK-801 was antagonized by tropisetron and zac opride and, to a lesser extent, by ketanserin, ritanserin and NAN-190, but not by WAY 100135, pindolol, metergoline or mianserin. Sulpiride and clozapine were able to inhibit the fluoxetine + MK-801 hyperlocomo tion. The hyperlocomotion induced by D-amphetamine or apomorphine was not modified by fluoxetine or citalopram. Fluoxetine increased the rel ease of dopamine (measured by a microdialysis method) in the striatum, induced by MK-801. The obtained results indicate that fluoxetine incr eases the MK-801-induced locomotor hyperactivity via activation of 5-H T3 receptors and, to a lesser degree, 5-HT2 ones.