In the present study, to clarify the role of the N-methyl-D-aspartate
(NMDA) receptor in the appearance of diazepam withdrawal signs, the ch
anges in [H-3]dizocilpine binding in several brain regions from diazep
am-withdrawn rats were investigated. Brain membranes were prepared 42-
45 h after termination of diazepam treatment when maximal withdrawal s
igns were shown. The B-max value for [H-3]dizocilpine binding was sign
ificantly increased in cerebrocortical, but not hippocampal and cerebe
llar, tissues from diazepam-withdrawn rats, while the K-d value did no
t change in any group. Together with our previous finding that NMDA re
ceptor antagonists potently suppress diazepam withdrawal signs, these
results suggest that the upregulation of the NMDA receptor in the cere
bral cortex may play an important role in the appearance of spontaneou
s withdrawal signs caused by discontinuation of chronic diazepam treat
ment. (C) 1998 Elsevier Science Ireland Ltd.