TY - JOUR
T1 - NMDA receptor antagonists potently suppress the spontaneous withdrawal signs induced by discontinuation of long-term diazepam treatment in Fischer 344 rats
AU - Tsuda, Makoto
AU - Suzuki, Tsutomu
AU - Misawa, Miwa
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid from The Tokyo Biochemical Research Foundation and a Research Grant (8A-5) for Nervous and Mental Disorders from the Ministry of Health and Welfare to T. Suzuki. We wish to thank Ms. Sachiko Komiya, Ms. Mio Sato and Ms. Miho Soma for their expert technical assistance.
PY - 1998/4/20
Y1 - 1998/4/20
N2 - The present study investigated the effects of the NMDA receptor antagonists dizocilpine (MK-801) and ifenprodil on the appearance of diazepam withdrawal signs caused by discontinuation of long-term diazepam treatment using a drug-admixed food (DAF) method in Fischer 344 rats. The total withdrawal score was significantly decreased by after-withdrawal treatment with dizocilpine or ifenprodil. Dizocilpine, in particular, markedly suppressed the motor withdrawal signs and body weight loss, while ifenprodil suppressed the motor and emotional withdrawal signs. Furthermore, the decrease in the food intake during withdrawal (anorexia) was significantly reduced by dizocilpine, but not by ifenprodil. These behavioral results indicated that the activation of NMDA receptors during withdrawal may play an important role in the appearance of withdrawal signs (in particular motor withdrawal signs) caused by discontinuation of chronic diazepam treatment, and that inhibitory agents for NMDA receptors may be effective in alleviation of the appearance of benzodiazepine withdrawal signs.
AB - The present study investigated the effects of the NMDA receptor antagonists dizocilpine (MK-801) and ifenprodil on the appearance of diazepam withdrawal signs caused by discontinuation of long-term diazepam treatment using a drug-admixed food (DAF) method in Fischer 344 rats. The total withdrawal score was significantly decreased by after-withdrawal treatment with dizocilpine or ifenprodil. Dizocilpine, in particular, markedly suppressed the motor withdrawal signs and body weight loss, while ifenprodil suppressed the motor and emotional withdrawal signs. Furthermore, the decrease in the food intake during withdrawal (anorexia) was significantly reduced by dizocilpine, but not by ifenprodil. These behavioral results indicated that the activation of NMDA receptors during withdrawal may play an important role in the appearance of withdrawal signs (in particular motor withdrawal signs) caused by discontinuation of chronic diazepam treatment, and that inhibitory agents for NMDA receptors may be effective in alleviation of the appearance of benzodiazepine withdrawal signs.
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U2 - 10.1016/S0006-8993(98)00052-3
DO - 10.1016/S0006-8993(98)00052-3
M3 - Article
C2 - 9593834
AN - SCOPUS:0032550205
SN - 0006-8993
VL - 790
SP - 82
EP - 90
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -