Subsensitivity to mitochondrial diazepam binding inhibitor receptor agonist FGIN-1-27-induced antiseizure effect in diazepam-withdrawn mice

Makoto Tsuda, Tsutomu Suzuki, Miwa Misawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We investigated the role of the mitochondrial diazepam binding inhibitor receptor (MDR) in diazepam-withdrawal seizure. In chronically vehicle- treated mice, the potent and selective MDR agonist FGIN-1-27 (N,N-di-n-hexyl 2-(4-fluorophenyl)indole-3-acetamide: 30 μg/mouse, i.c.v.) markedly increased the threshold for pentylenetetrazole (PTZ)-induced seizure. The antiseizure effect of FGIN-1-27 was blocked by pretreatment with the selective MDR antagonist PK11195 (1(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinolinecarboxamide). In chronically diazepam-treated mice, the seizure threshold of PTZ was decreased during diazepam withdrawal, indicating withdrawal hyperexcitability. Interestingly, FGIN-1-27 (30 μg/mouse, i.c.v.) failed to increase the seizure threshold of PTZ in diazepam-withdrawn mice, in contrast to its effect in chronically vehicle- treated mice. These findings suggest that the sensitivity of MDR-mediated pathways in the brain may be decreased during diazepam withdrawal.

Original languageEnglish
Pages (from-to)PL213-PL217
JournalLife Sciences
Volume62
Issue number14
DOIs
Publication statusPublished - Feb 27 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Subsensitivity to mitochondrial diazepam binding inhibitor receptor agonist FGIN-1-27-induced antiseizure effect in diazepam-withdrawn mice'. Together they form a unique fingerprint.

  • Cite this