Contribution of glutamate receptors to benzodiazepine withdrawal signs

Makoto Tsuda, Norifumi Shimizu, Tsutomu Suzuki

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)


Recent research has demonstrated that the receptor for glutamate, a major excitatory neurotransmitter, may play an important role in the expression of benzodiazepine withdrawal signs. This proposal is based on various observations. For example, antagonists for N-methyl-D-aspartate (NMDA), non-NMDA and metabotropic glutamate (mGlu) receptors can suppress the behavioral signs of benzodiazepine withdrawal in mice and rats. Furthermore, the NMDA receptor in the cerebrocortical area of diazepam-withdrawn rats is upregulated. Finally, the stimulation of phosphoinositide hydrolysis mediated by mGluR is enhanced in cerebrocortical slices from lorazepam-withdrawn mice. These findings show that the upregulation of signal transduction mediated by glutamate receptors during diazepam withdrawal plays a role in the neuroadaptive response responsible for the expression of diazepam withdrawal signs. Furthermore, ligands for glutamate receptors may be suitable targets for treating benzodiazepine withdrawal signs.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJapanese Journal of Pharmacology
Issue number1
Publication statusPublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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