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The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward

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Abstract

MK-801 is a ligand at phencyclidine recognition sites associated with NMDA-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate/aspartate (NMDA-type) receptors. Low doses (10–100 μg/kg IP) produced a dose-related and prolonged (>1 h) enhancement of variable-interval self-stimulation responding. Higher doses (300 μg/kg) caused flaccid ataxia and disrupted responding. Ketamine HCl (3.0–100 mg/kg IP), a dissociative anaesthetic binding to the phencyclidine site, produced a similar response pattern, but facilitation was less prolonged and occurred over a narrower dose range. Kynurenic acid (3.0–300 mg/kg IP), a nonselective competitive antagonist of glutamate receptors, produced only depression of responding, possibly the result of kynurenate-induced blockade of central kainate and/or quisqualate receptors. The behavioural stimulant effects of MK-801 appear to be an intrinsic and essential feature of selective NMDA antagonists, and these effects of MK-801 differ qualitatively and quantitatively from the well-known facilitatory effects of dopamine-dependent stimulants.

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Authors and Affiliations

  1. Experimental Psychology Laboratory, Institute of Neurology, Queen Square, WC1N 3BG, London, UK

    L. J. Herberg & I. C. Rose

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  1. L. J. Herberg
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  2. I. C. Rose
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Herberg, L.J., Rose, I.C. The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward. Psychopharmacology 99, 87–90 (1989). https://doi.org/10.1007/BF00634458

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  • DOI: https://doi.org/10.1007/BF00634458

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