Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine

Hiramatsu Masayuki Hiramatsu, Arthur K. Cho, Toshitaka Nabeshima

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

The behavioral and biochemical effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) were compared with those of phencyclidine (PCP). In the dose range used in this study, MK-801 (0.125-0.5 mg/kg i.p.) produced ataxia and other behavioral responses which were similar to PCP (5-10 mg/kg i.p.). However, turning and backpedalling induced by MK-801 were not dose-dependent and less intense at the dose producing approximately the same level of ataxia as PCP. Neurochemically, MK-801 (0.5 mg/kg i.p.) increased dopamine turnover in the cortex and striatum, but had no effect on 5-HT system. It was also 3.4 times less potent in inhibiting 5-HT uptake than PCP. These results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system.

Original languageEnglish
Pages (from-to)359-366
Number of pages8
JournalEuropean Journal of Pharmacology
Volume166
Issue number3
DOIs
Publication statusPublished - 03-08-1989
Externally publishedYes

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Phencyclidine
Dizocilpine Maleate
N-Methyl-D-Aspartate Receptors
Serotonin
Ataxia
Dopamine
Phencyclidine Receptors
Imines

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine",
abstract = "The behavioral and biochemical effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) were compared with those of phencyclidine (PCP). In the dose range used in this study, MK-801 (0.125-0.5 mg/kg i.p.) produced ataxia and other behavioral responses which were similar to PCP (5-10 mg/kg i.p.). However, turning and backpedalling induced by MK-801 were not dose-dependent and less intense at the dose producing approximately the same level of ataxia as PCP. Neurochemically, MK-801 (0.5 mg/kg i.p.) increased dopamine turnover in the cortex and striatum, but had no effect on 5-HT system. It was also 3.4 times less potent in inhibiting 5-HT uptake than PCP. These results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system.",
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Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. / Masayuki Hiramatsu, Hiramatsu; Cho, Arthur K.; Nabeshima, Toshitaka.

In: European Journal of Pharmacology, Vol. 166, No. 3, 03.08.1989, p. 359-366.

Research output: Contribution to journalArticle

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