PMID: 9550303Apr 29, 1998Paper

Hypersusceptibility to DMCM-induced seizures during diazepam withdrawal in mice: evidence for upregulation of NMDA receptors

Naunyn-Schmiedeberg's Archives of Pharmacology
M TsudaM Misawa

Abstract

The present study investigated the role of NMDA (N-methyl-D-aspartate) receptors in the hypersusceptibility to seizures induced by the benzodiazepine inverse agonist DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) during diazepam withdrawal in mice, using behavioral and biochemical approaches. The seizure threshold of DMCM was markedly decreased during diazepam withdrawal, reflecting withdrawal hyperexcitability in response to physical dependence. The decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was inhibited by the non-competitive NMDA receptor antagonists MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate; 50 microg/kg, s.c.) and ifenprodil (20 mg/kg, i.p.). The effective doses of these compounds were lower than those required to prevent DMCM-induced seizures in chronically vehicle-treated mice. Since MK-801 and ifenprodil do not only bind to NMDA receptors but also to sigma receptors, the present study also investigated the effects of sigma receptor ligands. The decrease in the seizure threshold of DMCM in diazepam-withdrawn mice was not modified by the sigma receptor agonist, (+)-pentazocine (5 mg/kg, s.c.), or the sigma receptor antagonist, NE-100 (N,N-...Continue Reading

Citations

Aug 17, 1999·European Journal of Pharmacology·B MalinowskaM Göthert
May 3, 2003·Pharmacology & Therapeutics·C Allison, J A Pratt
Apr 27, 2012·Advances in Pharmacological Sciences·Christiaan H Vinkers, Berend Olivier
Dec 2, 1999·Japanese Journal of Pharmacology·M TsudaT Suzuki
Jun 23, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Claire Allison, Judith A Pratt

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