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Augmentation of morphine-induced changes in brain monoamine metabolism after chronic naltrexone treatment

L Ahtee, LM Attila and KR Carlson

Department of Pharmacy, University of Helsinki, Finland.

To investigate the role of opioid mechanisms in the regulation of cerebral monoaminergic neurons, male Wistar rats were continuously infused with naltrexone via an Alzet osmotic minipump, or were sham- implanted, for 14 days. Twenty-four hours after removal of the pumps or sham implants, the rats were given s.c. morphine (3, 10 or 30 mg/kg) or saline and were sacrificed 2 hr postinjection. Eight brain regions were assayed for dopamine, 5-hydroxytryptamine, noradrenaline and their respective metabolites. Chronic naltrexone treatment per se caused only small changes in cerebral monoamines. Morphine elevated dose- dependently the cerebral concentrations of the acidic dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, as well as that of the 5-hydroxytryptamine metabolite, 5- hydroxyindoleacetic acid, and that of the noradrenaline metabolite, free 3-methoxy-4-hydroxyphenylethyleneglycol. In naltrexone-pretreated rats these elevations were significantly larger. Furthermore, in the naltrexone-pretreated rats 10 mg/kg of morphine significantly decreased the concentration of the dopamine metabolite 3-methoxytyramine both in the striatum and in the limbic forebrain, whereas in the control rats the 3-methoxytyramine content fell first after the 30-mg/kg dose and only in the striatum. Thus, both the stimulatory and the inhibitory effects of morphine on cerebral monoaminergic neurons seem to be potentiated by chronic naltrexone treatment. These data suggest that the activity of cerebral monoaminergic systems is to some degree regulated by an endogenous opioid input. When that input is chronically blocked, the basal metabolism of monoamines is not much altered but the systems' responsiveness to agonist challenge is increased.

Volume 255, Issue 2, pp. 803-808, 11/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.