Region-specific changes in [3H]dizocilpine binding in diazepam-withdrawn rats.
In the present study, to clarify the role of the N-methyl-D-aspartate (NMDA) receptor in the appearance of diazepam withdrawal signs, the changes in [3H]dizocilpine binding in several brain regions from diazepam-withdrawn rats were investigated. Brain membranes were prepared 42-45 h after termination of diazepam treatment when maximal withdrawal signs were shown. The Bmax value for [3H]dizocilpine binding was significantly increased in cerebrocortical, but not hippocampal and cerebellar, tissues from diazepam-withdrawn rats, while the Kd value did not change in any group. Together with our previous finding that NMDA receptor antagonists potently suppress diazepam withdrawal signs, these results suggest that the upregulation of the NMDA receptor in the cerebral cortex may play an important role in the appearance of spontaneous withdrawal signs caused by discontinuation of chronic diazepam treatment.
Tsuda
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Suzuki
T
T
Misawa
M
M
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003975:Diazepam / Q000009:adverse effects*; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003975:Diazepam