Effects of D-cycloserine and (+)-HA-966 on the locomotor stimulation induced by NMDA antagonists and clonidine in monoamine-depleted mice.
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.
Carlsson
M L
ML
Department of Pharmacology, University of Göteborg, Sweden.
Engberg
G
G
Carlsson
A
A
D000495:Allosteric Site; D000818:Animals; D015306:Biogenic Monoamines; D003000:Clonidine / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D011760:Pyrrolidinones / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D018009:Receptors, Glycine / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
D015306:Biogenic Monoamines; D011760:Pyrrolidinones; D018341:Receptors, Adrenergic, alpha-2; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D003523:Cycloserine; C001369:1-hydroxy-3-amino-2-pyrrolidone; D003000:Clonidine