EFFECTS OF CHRONIC MORPHINE TREATMENT ON CATECHOLAMINES CONTENT AND MECHANICAL RESPONSE IN THE RAT HEARTS

Our investigation was aimed at elucidating if the chronic administrati on and withdrawal of a preferential mu-agonist, morphine, induce chang es on the heart catecholaminergic neuronal activity. With this purpose the effects of morphine or naloxone (preferentially mu-antagonist) on noradrenaline, adrenaline or dopamine (DA) content and the mechanical response of the left atria were studied in chronically placebo- or mo rphine-treated rats (implanted s.c. with pellets for 7 days). In morph ine-treated rats, a challenge dose of morphine (30 mg/kg i.p.) increas ed the auricular noradrenaline, adrenaline and DA content and decrease d dihydroxy phenyl acetic acid/DA ratio; these changes were accompanie d 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 decr ease 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 excitator y reactions to naloxone-precipitated withdrawal and suggest that the c hanges observed in the heart by the chronic administration of morphine and after naloxone precipitated withdrawal are mostly mediated by the catecholaminergic system.