Open AccessContribution of Glutamate Receptors to Benzodiazepine Withdrawal Signs.
Author(s) -
Makoto Tsuda,
Norifumi Shimizu,
Tsutomu Suzuki
Publication year - 1999
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.81.1
Subject(s) - metabotropic glutamate receptor , glutamate receptor , benzodiazepine , nmda receptor , diazepam , pharmacology , metabotropic receptor , metabotropic glutamate receptor 2 , receptor , gabaa receptor , chemistry , stimulation , neuroscience , kindling , metabotropic glutamate receptor 1 , long term depression , downregulation and upregulation , psychology , biology , ampa receptor , biochemistry , gene
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 Furthermore, the NMDA receptor in the cerebrocortical area of diazepam-withdrawn rats is upregulated.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the stimulation of phosphoinositide hydrolysis mediated by mGluR is enhanced in cerebrocortical slices from lorazepam-withdrawn mice.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.