INHIBITORY EFFECT OF THE NMDA RECEPTOR ANTAGONIST, DIZOCILPINE (MK-801), ON THE DEVELOPMENT OF MORPHINE DEPENDENCE
スポンサーリンク
概要
- 論文の詳細を見る
We investigated the effect of a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-iminehydrogen maleate (dizocilpine, MK-801), on hippocampal norepinephrine release in morphine-treated rats in order to clarify the relationship between NMDA receptors and the development of morphine dependence. Naloxone hydrochloride injected subcutaneously (s.c.) into morphine-dependent rats, induced an immediate increase in hippocampal norepinephrine release, which was associated with a typical morphine withdrawal syndrome. The increased norepinephrine levels persisted for at least 2 hr, even after the disappearance of the behavioral withdrawal syndrome. This striking effect of naloxone on hippocampal norepinephrine release was dependent on the duration of the intraberebroventricular (i.c.v.) morphine infusion. Pretreatment with dizocilpine (s.c.) before naloxone challenge reduced the rate of the rise in hippocampal norepinephrine release induced by naloxone in morphine-treated rats. Concurrent infusion (i.c.v.) of dizocilpine and morphine decreased the level of hippocampal norepinephrine release after a naloxone challenge. Both pretreatment with dizocilpine (s.c.) before naloxone injection and infusion (i.c.v.) of dizocilpine suppressed rearing and teeth-chattering signs, but not wet-dog shakes in morphine-treated rats. These results suggest that dizocilpine attenuates the development of morphine dependence through NMDA receptors, and thus that interaction between opioid receptors and NMDA receptors may be involved in the development of morphine dependence.
- 日本トキシコロジー学会の論文
- 1996-05-25
著者
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FUKUDA Hideomi
Department of Pharmacology, College of Pharmacy, Nihon University
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Fukuda H
Department Of Toxicology And Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Fukuda Hideomi
Department Of Pharmacology College Of Pharmacy Nihon University
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Fukuda Hitoshi
Research Laboratories Toyama Chemical Co. Ltd.
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Fukuda H
Clinical Research Department Toyama Chemical Co. Ltd.
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MAKIMURA Mizue
Department of Pharmacology, College of Pharmacy, Nihon University
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SUGIMOTO Hideya
Department of Pharmacology, College of Pharmacy, Nihon University
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SHINOMIYA Kazufusa
Department of Analytical Chemistry, College of Pharmacy, Nihon University
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KABASAWA Yozo
Department of Analytical Chemistry, College of Pharmacy, Nihon University
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Kabasawa Y
Department Of Analytical Chemistry College Of Pharmacy Nihon University
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Makimura M
Department Of Pharmacology College Of Pharmacy Nihon University
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Makimura Mizue
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences University Of Tokyo:(present
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Sugimoto Hideya
Department Of Pharmacology College Of Pharmacy Nihon University
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Shinomiya K
Department Of Analytical Chemistry College Of Pharmacy Nihon University
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Shinomiya Kazufusa
Department Of Analytical Chemistry College Of Pharmacy Nihon University
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FUKUDA Hideomi
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University
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