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

Eur J Pharmacol. 1989 Aug 3;166(3):359-66. doi: 10.1016/0014-2999(89)90346-4.

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 systems. 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Ataxia / chemically induced
  • Behavior, Animal / drug effects*
  • Biogenic Monoamines / metabolism
  • Brain Chemistry / drug effects*
  • Dibenzocycloheptenes / pharmacology*
  • Dizocilpine Maleate
  • Male
  • Motor Activity / drug effects
  • Phencyclidine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Serotonin / metabolism
  • Stereotyped Behavior / drug effects
  • Time Factors

Substances

  • Anticonvulsants
  • Biogenic Monoamines
  • Dibenzocycloheptenes
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Serotonin
  • Dizocilpine Maleate
  • Phencyclidine