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
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.