Effects of an NMDA-receptor antagonist, MK-801, on central locomotor programming in the rabbit

Exp Brain Res. 1991;86(2):393-401. doi: 10.1007/BF00228963.

Abstract

NMDA has been shown to disclose spinal fictive locomotor activity in various in vitro preparations. In the present work the NMDA-mediated effects of endogenously released excitatory aminoacids (EAA) on fictive locomotion in the adult rabbit preparation were assessed in vivo using systemic injections of a non competitive NMDA-antagonist, MK-801. In acute low spinal and curarized preparations, the amplitude of the "spontaneous" fictive locomotor activities recorded from hindlimb muscle nerves after nialamide-DOPA pretreatment was much decreased in flexor and extensor nerves after MK-801 administration (0.25 mg/kg i.v.) whereas the locomotor period increased slightly. The more potent locomotor bursts, evoked by repetitive sural nerve stimulation at 10 Hz during 10 s, were differently affected after MK-801: the main effect was a lengthening of the locomotor period and a less drastic drop in the burst amplitude. These changes in the burst period were maximal for activities evoked by A fibre group stimulation (+100%) and less when C fibres were recruited (+70%). In decerebrate curarized preparations where the locomotor sequences were evoked either by sural nerve stimulation or by stimulation of the mesencephalic locomotor region, MK-801 (0.25 mg/kg i.v.) caused the same drop in burst amplitude (by at least 50%) as in the spinal preparation but, in contrast, it reinforced rhythmic bursting: this was revealed by a clear shortening (up to -65%) of the locomotor period and by the prolongation of rhythmic bursting after stimulation. All these effects obtained in decerebrate preparations were maximal 20-30 min after MK-801 injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Amino Acids / physiology
  • Animals
  • Blood Pressure / drug effects
  • Decerebrate State / physiopathology
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Locomotion / drug effects*
  • Rabbits
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Reflex / drug effects

Substances

  • Amino Acids
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate