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Antagonists at the NMDA recognition site and Mockers of the associated ion channel induce spontaneous tail-flicks in the rat

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Abstract

The non-competitive N-methyl-D-aspartate (NMDA) antagonists (channel blockers), MK 801, phencyclidine (PCP) and ketamine induced spontaneous tail-flicks in rats. Their order of relative potency (MK 801 > PCP > ketamine) corresponds to their relative affinities for the ion channel coupled to NMDA receptors. Drugs interacting with their other potential targets (σ-receptors as well as dopamine, serotonin and noradrenaline uptake sites) failed to induce spontaneous tail-flicks. In addition, the catecholamine stimulants, methylphenidate and cocaine were inactive. CPP and CGS 19755, antagonists at the NMDA recognition site, also dose dependently elicited spontaneous tail-flicks: their maximal effect was equal to that of the channel blockers. In contrast, HA-966 and ifenprodil, putative antagonists at the glycine and polyamine recognition sites, respectively, failed to elicit spontaneous tail-flicks. These data demonstrate that both antagonists of the NMDA recognition site and non-competitive blockers of the associated channel induce spontaneous tail-flicks in rats.

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Cited by (7)

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    This response was mimicked by the NMDA receptor recognition site antagonist, CPP, but not by the glycine B ligand, (+)-HA966, nor by drugs acting at polyamine sites or other potential modulatory sites of the NMDA receptor complex (Millan, 1991). Moreover, AMPA/kainate receptor antagonists and a broad range of pharmacologically diverse motor stimulant drugs are likewise ineffective in provoking spontaneous tail-flick: notably, catecholamine releasers/uptake inhibitors, such as cocaine; direct dopamine receptor agonists, such as apomorphine; μ-opioids such as morphine; hallucinogens such as mescaline; GABA receptor antagonists, such as bicucculine; adenosine receptor antagonists, such as caffeine and muscarinic receptor antagonists, such as scopolamine (Millan, 1991; Millan et al., 1991). These observations suggest that spontaneous tail-flick may provide a useful model for the detection and characterization of drug activity at NMDA receptors in vivo.

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