The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice

J Neural Transm. 1989;75(3):221-6. doi: 10.1007/BF01258633.


It was shown in the present study that the selective non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] caused a pronounced and dose-dependent increase in locomotion in mice pretreated with a combination of reserpine and alpha-methyl-para-tyrosine. Haloperidol pretreatment did not antagonize the MK-801-induced stimulation of locomotion. The findings are discussed in relation to the concept of a corticostriatothalamocortical negative feedback loop serving to protect the cortex from an overload of information and hyperarousal. Such a feedback loop would encompass i.a. corticostriatal glutamatergic neurons and it would be modulated by mesencephalostriatal dopaminergic neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biogenic Monoamines / physiology*
  • Dibenzocycloheptenes / pharmacology*
  • Dizocilpine Maleate
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology
  • Male
  • Methyltyrosines / pharmacology*
  • Mice
  • Motor Activity / drug effects*
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Reserpine / pharmacology
  • alpha-Methyltyrosine


  • Biogenic Monoamines
  • Dibenzocycloheptenes
  • Methyltyrosines
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • alpha-Methyltyrosine
  • Dizocilpine Maleate
  • Reserpine
  • Haloperidol