Contribution of glutamate receptors to benzodiazepine withdrawal signs

Jpn J Pharmacol. 1999 Sep;81(1):1-6. doi: 10.1254/jjp.81.1.


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 Furthermore, the NMDA receptor in the cerebrocortical area of diazepam-withdrawn rats is upregulated.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the stimulation of phosphoinositide hydrolysis mediated by mGluR is enhanced in cerebrocortical slices from lorazepam-withdrawn mice.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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Anxiety Agents / adverse effects*
  • Benzodiazepines
  • Humans
  • Receptors, Glutamate / physiology*
  • Substance Withdrawal Syndrome / etiology*
  • Substance Withdrawal Syndrome / metabolism*


  • Anti-Anxiety Agents
  • Receptors, Glutamate
  • Benzodiazepines