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

Abstract

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.

• Authors: M L Carlsson, G Engberg, A Carlsson
• Journal: Journal of neural transmission. General section (J Neural Transm Gen Sect) Vol. 95 Issue 3 Pg. 223-33 ( 1994) Austria
• PMID: 7865177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)