Acceleration of cerebral noradrenaline turnover after morphine withdrawal and its retardation by acute morphine administration in rats

Abstract

To clarify the effects of withdrawal from chronic morphine treatment on cerebral noradrenaline (NA) turnover, we have measured the alpha-methyl-p-tyrosine (alpha MT)-induced depletion of NA in five brain areas of male Wistar rats given morphine twice daily for 40 or 60 days. After the last morphine dose (50 or 70 mg/kg) the rats were withdrawn for 1, 2 or 4 days. In order to study the development of tolerance a challenge dose of 10 mg/kg of morphine was given to some of the rats. Withdrawal of morphine accelerated the alpha MT-induced NA depletion clearly in the hemispheres and the lower brain stem and slightly in the diencephalon. The acceleration was more pronounced in the brains of rats treated for 60 days than of those treated for 40 days. In the hemispheres the acceleration of NA depletion occurred at 1 and 2 days, in the diencephalon at 2 days, and in the lower brain stem at 2 and 4 days after morphine withdrawal. The most pronounced acceleration of NA depletion coincided with the maximum withdrawal-induced weight loss. The challenge dose of morphine clearly retarded the alpha MT-induced NA depletion in the hemispheres of control rats treated chronically with saline. This retardation was even more pronounced in rats withdrawn from chronic morphine treatment for 1 or 2 days. The challenge dose slightly accelerated the alpha MT-induced NA depletion in the lower brain stem of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Differences in Cerebral Noradrenaline Turnover in Mice Withdrawn from Repeated Morphine Treatment and Tolerance to the Effects of Acute Morphine

“…In mice acute morphine accelerates noradrenaline (NA) turnover in all brain areas and tolerance develops towards these effects (Smith et al 1970(Smith et al & 1972Rosenman & Smith 1972;Bloom et al 1976;Kempf et al 1976;Attila et al 1987;Etemadzadeh 1993). In rats acute morphine elevates sulphated 3-methoxy-4-hydroxyphenylethylene glycol (MO-PEG) concentration in all brain areas as well as enhances the a-methyl-p-tyrosine (aMT)-induced NA depletion in the lower brain stem but retards it in the cortical areas; however, tolerance develops only to the NA turnover enhancing effects of acute morphine (Roffman et al 1977;Attila & Ahtee 1983Ahtee et al 1989;Attila 1989). While Author for correspondence: Liisa Ahtee, Division of Pharmacology and Toxicology, Department of Pharmacy, PO.…”

“…Morphine withdrawal clearly increases cerebral NA turnover and release in rats (Gunne et al 1969;Gramsch & Blasig 1976;Crawley et al 1979;Swann et al 1983;Attila & Ahtee 1983Ahtee et al 1989) but in mice the reports are few and the results controversial: no increase of the cortical free MOPEG concentration (Funada et al 1993), increase of the aMT-induced NA depletion only in some brain nuclei (Kovacs et al 1983) or even retardation of NA synthesis rate in the whole brain (Rosenman & Smith 1972;Smith et al 1972). Futher, there is no thorough study about the effects of morphine withdrawal and challenge on free MOPEG, the main metabolite of NA and thus a functional index of NA turnover in the mouse brain (Sharman 1969;Ceasar et al 1974;Heal et al 1989).…”

Differences in the Effects of Morphine on the α‐Methyl‐p‐tyrosine‐induced Depletion of Dopamine and Noradrenaline in Various Areas of the Mouse Brain

“…In rat brain morphine enhances the aMT-induced depletion of NA and elevates the concentration of 3-methoxy-4-hydroxyphenylglycol only in large doses and not in all brain areas (Gunne et al 1969;Sugrue 1974;Papeschi et al 1975;Paalzow & Paalzow 1975;Gomes et al 1976;Roffman et al 1977;Dettmar et al 1981;Tanaka et al 1983). Furthermore, we found that morphine clearly retarded the aMT-induced NA depletion in the cortical hemispheres of rats (Attila et al 1981;Attila & Ahtee 1983& 1984a. Several investigators found that morphine increases NA turnover in mouse whole brain (Smith et al 1972;Bloom et al 1976;Cott & Engel 1977).…”

“…The method described by Keller et al (1976) was slightly modified. For details see Attila & Ahtee (1984a). One-way ANOVA followed by Student's t-test (pooled variance) was used when comparing the means of morphine-treated and aMT-treated mice.…”

Plasma Catecholamine Concentrations During Morphine Withdrawal in Conscious Guinea‐pigs

“…Central catecholaminergic neuronal systems have been implicated in opiate dependence and withdrawal in many studies (for review see Redmond & Krystal 1984). However, the effects of opiate withdrawal on the central nervous system are complex and regional differences in brain noradrenaline (NA) turnover after morphine withdrawal have been found (Attila & Ahtee 1984). The relation-ship between central catecholaminergic neuronal systems in opiate withdrawal and the peripheral sympathetic nervous system is not clear.…”