TY - JOUR
T1 - Recovery of decreased seizure threshold for pentylenetehazole during diazepam withdrawal by NMDA receptor antagonists
AU - Tsuda, Makoto
AU - Suzuki, Tsutomu
AU - Misawa, Miwa
N1 - Funding Information:
This work was supported in part by a Research Grant (8A-5) for Nervous and Mental Disorders from the Ministry of Health and Welfare to T.S. We wish to thank Mr. Norifumi Shimizu, Mr. Yoshinori Yajima and Ms. Yuko Sugano for their expert technical assistance.
PY - 1997/4/11
Y1 - 1997/4/11
N2 - The effects of several NMDA receptor antagonists on pentylenetetrazole-induced diazepam-withdrawal seizure were examined in mice. The decrease in the seizure threshold for pentylenetetrazole during diazepam withdrawal was inhibited by pretreatment with MK-801 ((+)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate), 7-chlorokynurenic acid and ifenprodil. Furthermore, MK-801 and ifenprodil, at doses which did not affect the threshold of pentylenetetrazole-induced seizure in control mice, also significantly suppressed the decrease in the seizure threshold during diazepam withdrawal, whereas 7-chlorokynurenic acid did not. These findings suggest that overactivity of an ion channel site and an ifenprodil binding site on the NMDA receptor may play an important role in the hypersensitivity of pentylenetetrazole-induced seizure in diazepam-withdrawn mice.
AB - The effects of several NMDA receptor antagonists on pentylenetetrazole-induced diazepam-withdrawal seizure were examined in mice. The decrease in the seizure threshold for pentylenetetrazole during diazepam withdrawal was inhibited by pretreatment with MK-801 ((+)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cycloheptan-5,10-imine maleate), 7-chlorokynurenic acid and ifenprodil. Furthermore, MK-801 and ifenprodil, at doses which did not affect the threshold of pentylenetetrazole-induced seizure in control mice, also significantly suppressed the decrease in the seizure threshold during diazepam withdrawal, whereas 7-chlorokynurenic acid did not. These findings suggest that overactivity of an ion channel site and an ifenprodil binding site on the NMDA receptor may play an important role in the hypersensitivity of pentylenetetrazole-induced seizure in diazepam-withdrawn mice.
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U2 - 10.1016/S0014-2999(97)00152-0
DO - 10.1016/S0014-2999(97)00152-0
M3 - Article
C2 - 9137914
AN - SCOPUS:0031564604
VL - 324
SP - 63
EP - 66
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -