Vol. 280, Issue 1, 32-37, 1997

Effects of Chronic Morphine Treatment on Catecholamines Content and Mechanical Response in the Rat Hearts¹

J. V. Rabadán, M. V. Milanés and M. L. Laorden

Department of Physiology and Pharmacology. Unit of Pharmacology, University School of Medicine, Murcia, Spain

Our investigation was aimed at elucidating if the chronic administration and withdrawal of a preferential µ-agonist, morphine, induce changes on the heart catecholaminergic neuronal activity. With this purpose the effects of morphine or naloxone (preferentially µ-antagonist) on noradrenaline, adrenaline or dopamine (DA) content and the mechanical response of the left atria were studied in chronically placebo- or morphine-treated rats (implanted s.c. with pellets for 7 days). In morphine-treated rats, a challenge dose of morphine (30 mg/kg i.p.) increased the auricular noradrenaline, adrenaline and DA content and decreased dihydroxy phenyl acetic acid/DA ratio; these changes were accompanied by a decrease in the force of contraction in the isolated left atria. No changes were observed in placebo-treated rats. The administration of naloxone (1 mg/kg s.c.) to morphine-treated animals induced a decrease on the auricular content of noradrenaline, adrenaline and DA and an increase in dihydroxy phenyl acetic acid/DA ratio. The study of the mechanical response to naloxone in the isolated left atria showed an enhancement in the force of contraction in preparations from morphine-treated rats, whereas in the placebo-pelleted rats naloxone induced a decrease in this parameter. These findings demonstrate that the heart of rats that had received chronic morphine-treatment exhibit excitatory reactions to naloxone-precipitated withdrawal and suggest that the changes observed in the heart by the chronic administration of morphine and after naloxone precipitated withdrawal are mostly mediated by the catecholaminergic system.