The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist.
It was found previously that the MK-801 (an uncompetitive NMDA receptor antagonist)-induced locomotor hyperactivity in rats was potently increased by antidepressant drugs. The present paper analysed the locomotor hyperactivity induced by combined treatment with fluoxetine + MK-801 in male Wistar rats. The MK-801 hyperactivity was increased by citalopram (the latter effect was prevented by zacopride and ketanserin), sertraline, p-chloramphetamine, 8-OH-DPAT and TFMPP. The hyperlocomotion caused by fluoxetine + MK-801 was antagonized by tropisetron and zacopride 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 hyperlocomotion. The hyperlocomotion induced by D-amphetamine or apomorphine was not modified by fluoxetine or citalopram. Fluoxetine increased the release of dopamine (measured by a microdialysis method) in the striatum, induced by MK-801. The obtained results indicate that fluoxetine increases the MK-801-induced locomotor hyperactivity via activation of 5-HT3 receptors and, to a lesser degree, 5-HT2 ones.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Rogóz
Z
Z
Skuza
G
G
Wedzony
K
K
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D016291:Dizocilpine Maleate; D004298:Dopamine; D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D005473:Fluoxetine; D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors