Effects of D-cycloserine and (+)-HA-966 on the locomotor stimulation induced by NMDA antagonists and clonidine in monoamine-depleted mice

J Neural Transm Gen Sect. 1994;95(3):223-33. doi: 10.1007/BF01271568.


We have previously observed that an N-methyl-D-aspartate (NMDA) antagonist in combination with the alpha 2-adrenoceptor agonist clonidine produces a marked locomotor stimulation in monoamine-depleted mice. In this paper we report on how the partial glycine agonists D-cycloserine (high intrinsic activity) and (+)-HA-966 [(+)-3-amino-1-hydroxypyrrolid-2-one; low intrinsic activity] affect this response; the interaction with both an uncompetitive and a competitive NMDA antagonist was investigated. (+)-HA-966 was found to counteract the locomotor stimulation produced by clonidine combined with either an uncompetitive (MK-801 = dizocilpine) or a competitive [D-CPPene = 3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid] NMDA antagonist. D-cycloserine potentiated the locomotor stimulation produced by either NMDA antagonist combined with clonidine, although statistical significance was achieved only in the case of MK-801. If the present hyperactivity model has any relevance for psychosis the prediction based on the present results would be that d-cycloserine, contrary to current hopes, might not be so effective in schizophrenia, whereas (+)-HA-966 might be an interesting candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Site
  • Animals
  • Biogenic Monoamines*
  • Clonidine / pharmacology*
  • Cycloserine / pharmacology*
  • Dose-Response Relationship, Drug
  • Mice
  • Motor Activity / drug effects*
  • N-Methylaspartate / antagonists & inhibitors*
  • Pyrrolidinones / pharmacology*
  • Receptors, Adrenergic, alpha-2 / physiology
  • Receptors, Glycine / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology


  • Biogenic Monoamines
  • Pyrrolidinones
  • Receptors, Adrenergic, alpha-2
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • Cycloserine
  • 1-hydroxy-3-amino-2-pyrrolidone
  • Clonidine