Jv. Rabadan et al., EFFECTS OF CHRONIC MORPHINE TREATMENT ON CATECHOLAMINES CONTENT AND MECHANICAL RESPONSE IN THE RAT HEARTS, The Journal of pharmacology and experimental therapeutics, 280(1), 1997, pp. 32-37
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.