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The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist

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Summary

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.

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  1. J. Maj

    Present address: Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

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  1. Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

    Z. Rogóż, G. Skuza & K. Wędzony

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  3. G. Skuza
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  4. K. Wędzony
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Maj, J., Rogóż, Z., Skuza, G. et al. The synergistic effect of fluoxetine on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist. J. Neural Transmission 103, 131–146 (1996). https://doi.org/10.1007/BF01292622

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  • DOI: https://doi.org/10.1007/BF01292622

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