Reversion of beta 25-35-amyloid peptide-induced amnesia by NMDA receptor-associated glycine site agonists.
The effects of D-cycloserine (DCS), a N-methyl-D-aspartate receptor-associated glycine site agonist, and milacemide (MIL), a glycine prodrug, were examined on learning impairments induced by administration of beta 25-35-amyloid peptide (3 nmol i.c.v.). Mice were examined for spontaneous alternation and step-down passive avoidance, 7 and 14 days after beta 25-35, respectively. The beta 25-35-induced deficits were reversed by DCS, 1-30 mg/kg i.p., or MIL, 3-100 mg/kg i.p., each drug being ineffective on control mice behaviours. These observations strengthen the therapeutic potential of glycine site agonists against the memory impairments induced by beta-amyloid peptides.
Maurice
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T
INSERM U. 336, Développement, Plasticité et Vieillissement du Système Nerveux, Ecole Nationale Supérieure de Chimie, Montpellier, France. maurice@cit.enscm.fr
Lockhart
B P
BP
Su
T P
TP
Privat
A
A
D000081:Acetamides / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites / Q000502:physiology; D003523:Cycloserine / Q000494:pharmacology; D005998:Glycine / Q000819:agonists*; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000737:chemistry
D000081:Acetamides; D016229:Amyloid beta-Peptides; D000963:Antimetabolites; D008996:Monoamine Oxidase Inhibitors; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C039332:milacemide; D003523:Cycloserine; D005998:Glycine