NMDA receptor antagonists potently suppress the spontaneous withdrawal signs induced by discontinuation of long-term diazepam treatment in Fischer 344 rats

Tsuda Makoto, Tsutomu Suzuki, Miwa Misawa

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)82-90
Number of pages9
JournalBrain Research
Volume790
Issue number1-2
DOIs
Publication statusPublished - Apr 20 1998
Externally publishedYes

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Dizocilpine Maleate
Inbred F344 Rats
Diazepam
N-Methyl-D-Aspartate Receptors
Anorexia
Benzodiazepines
Weight Loss
Eating
Body Weight
Food
ifenprodil
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

NMDA receptor antagonists potently suppress the spontaneous withdrawal signs induced by discontinuation of long-term diazepam treatment in Fischer 344 rats. / Makoto, Tsuda; Suzuki, Tsutomu; Misawa, Miwa.

In: Brain Research, Vol. 790, No. 1-2, 20.04.1998, p. 82-90.

Research output: Contribution to journalArticle

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