Autoradiographic study of NMDA-displaceable [3H]glutamate and [3H]MK-801 binding during butorphanol withdrawal in the rat brain.
Influences of continuous administration of butorphanol on the autoradiography of [3H]glutamate binding and [3H]MK-801 binding were investigated to study the effects of butorphanol withdrawal on NMDA receptors. Rats were administered butorphanol (26 nmol microl(-1) h(-1)) by continuous intracerebroventricular (i.c.v.) infusion through pre-implanted cannula connected to osmotic mini-pumps for 3 days. Rats were then sacrificed at 2, 7, and 24 h after discontinuation of butorphanol infusion. [3H]MK-801 binding was slightly increased in the cortical area, hippocampus, and cerebellum in 2, 7, and 24 h withdrawal groups and was shown most significant increase in the 7 h withdrawal group. NMDA-displaceable [3H]glutamate binding was markedly increased in the cortical area, striatum, septum, hippocampus, thalamus, and cerebellum in 7 h withdrawal group and was significantly increased in the striatum, hippocampus, and thalamus in 24 h withdrawal group. These results demonstrate that the development of butorphanol withdrawal is more prominent by 7 h after discontinuation of butorphanol infusion and suggest that NMDA binding sites at NMDA receptors may play more important role in the development of butorphanol withdrawal than that of channel blocking sites.
Jang
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
Park
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Rockhold
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D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects*; D002077:Butorphanol / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D014316:Tritium
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D014316:Tritium; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D002077:Butorphanol