Anxiolytic-like effects of N-methyl-D-aspartate-associated glycine receptor ligands in the rat potentiated startle test

Eur J Pharmacol. 1993 Dec 7;250(2):317-24. doi: 10.1016/0014-2999(93)90397-z.

Abstract

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.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Ligands
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Glycine / antagonists & inhibitors
  • Receptors, Glycine / drug effects*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Reflex, Startle / drug effects*

Substances

  • Anti-Anxiety Agents
  • Ligands
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate