Abstract
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.
Footnotes
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Send reprint requests to: Dr. M. V. Milanés, Departamento de Farmacología, Facultad de Medicina, 30071 Murcia, España.
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↵1 This work was supported by FIS (90/0460) and DGICYT (PB93/1128).
- Abbreviations:
- NA
- noradrenaline
- A
- adrenaline
- DA
- dopamine
- DOPAC
- dihydroxy phenyl acetic acid
- DHBA
- 3,4-dihydroxy-benzylamine
- MPLM
- myenteric plexus-longitudinal muscle
- Received January 2, 1996.
- Accepted August 29, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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