CONCURRENT NIMODIPINE ATTENUATES THE WITHDRAWAL SIGNS AND THE INCREASE OF CEREBRAL DIHYDROPYRIDINE BINDING AFTER CHRONIC MORPHINE TREATMENTIN RATS

Citation
A. Zharkovsky et al., CONCURRENT NIMODIPINE ATTENUATES THE WITHDRAWAL SIGNS AND THE INCREASE OF CEREBRAL DIHYDROPYRIDINE BINDING AFTER CHRONIC MORPHINE TREATMENTIN RATS, Naunyn-Schmiedeberg's archives of pharmacology, 347(5), 1993, pp. 483-486
Citations number
25
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00281298
Volume
347
Issue
5
Year of publication
1993
Pages
483 - 486
Database
ISI
SICI code
0028-1298(1993)347:5<483:CNATWS>2.0.ZU;2-Q
Abstract
The effect of chronic administration of dihydropyridine calcium channe l antagonist nimodipine (1 mg/kg/day) given concurrently with morphine on the signs of morphine withdrawal and on the [H-3]nitrendipine bind ing in the rat brain has been investigated. Chronic morphine administr ation in increasing daily doses from 20 mg/kg to 70 mg/kg for 24 days and consequent withdrawal for 24 h induced loss of body weight, wet do g shakes, episodes of writhing and yawning behaviour. The density of [ H-3]nitrendipine binding was elevated in the cortex and limbic structu res but not in the striatum after chronic morphine treatment. Chronic concurrent administration of nimodipine prevented the loss of body wei ght and reduced the scores of wet dog shakes and writhing, but did not affect yawning behaviour at 24 h after morphine withdrawal. The concu rrent nimodipine treatment also prevented the rise in the density of c entral dihydropyridine binding sites which occurred upon chronic morph ine treatment. These results suggest that chronic nimodipine treatment attenuates the development of the withdrawal signs which occur upon t he termination of chronic morphine treatment by preventing the up-regu lation of the central dihydropyridine-sensitive binding sites.