Contribution of glutamate receptors to benzodiazepine withdrawal signs.
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 Furthermore, the NMDA receptor in the cerebrocortical area of diazepam-withdrawn rats is upregulated.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the stimulation of phosphoinositide hydrolysis mediated by mGluR is enhanced in cerebrocortical slices from lorazepam-withdrawn mice.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.
Tsuda
M
M
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Shimizu
N
N
Suzuki
T
T
D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001569:Benzodiazepines; D006801:Humans; D017470:Receptors, Glutamate / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D017470:Receptors, Glutamate; D001569:Benzodiazepines