Jpn. J. Pharmacol. 81 (1), 1 - 6 (1999)

-Current Perspective-
Contribution of Glutamate Receptors to Benzodiazepins Withdrawal Signs

Makoto Tsuda1, Norifumi Shimizu2 and Tsutomu Suzuki3,*

1Section of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 1 - 18 - 1 Kamiyoga, Setagaya-ku, Tokyo 158 - 8501, Japan
2Department of Pharmacology, Wakayama Medical College, 811 - 1 Kimiidera, Wakayama-city, Wakayama 641 - 0012, Japan
3Department of Toxicology, School of Pharmacy, Hoshi University, 2 - 4 - 41 Ebara, Shinagawa-ku, Tokyo 142 - 8501, Japan
* To whom correspondence should be addressed.

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 Furthermore, the NMDA receptor in the cerebrocortical area of diazepam-withdrawn rats is upregulated.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the stimulation of phosphoinositide hydrolysis mediated by mGluR is enhanced in cerebrocortical slices from lorazepam-withdrawn mice.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

Benzodiazepine, Withdrawal sign, Glutamate receptor

Copyrightę The Japanese Pharmacological Society 1999

[Back to TOC]