Anxiolytic-like effects of N-methyl-D-aspartate-associated glycine receptor ligands in the rat potentiated startle test.
Competitive and non-competitive NMDA receptor complex antagonists have been shown to be active in various models of anxiolytic activity. This study examined the effects of ligands at the NMDA receptor-associated glycine site and two competitive NMDA receptor antagonists on the fear-potentiated startle response model for anxiolytic activity. The results show that the NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (30 mg/kg) and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (3 mg/kg), the glycine receptor antagonist 7-chlorokynurenate (100 mg/kg), and the glycine receptor partial agonists 3-amino-1-hydroxy-2-pyrrolidinone ((+)-HA-966) (30 mg/kg), 1-aminocyclopropane carboxylate (200-500 mg/kg) and D-cycloserine (30-300 mg/kg) blocked the potentiated startle effect. These results extend the findings of earlier studies showing anxiolytic-like effects of NMDA antagonists and glycine receptor ligands by demonstrating their effectiveness in the rat potentiated startle paradigm. These results also demonstrate the anxiolytic potential of D-cycloserine.
Anthony
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Department of Neurological Diseases Research, Searle, Skokie, IL 60077.
Nevins
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ME
D000161:Acoustic Stimulation; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D008024:Ligands; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate