Morphine and morphiceptin increase the threshold for epinephrine-induced cardiac arrhythmias in the rat through brain mu opioid receptors.
1. To determine whether morphine modulates the development of cardiac arrhythmias through mu opioid receptors by an action within the central nervous system (CNS). Catecholamine-induced ventricular arrhythmias were produced, in the rat, by continuous infusion of epinephrine at incremental doses until the development of fatal arrhythmias, usually ventricular fibrillation. 2. Morphine, 0.1 mg/kg i.v., significantly suppressed (P < 0.05) the development of epinephrine-induced arrhythmias compared with the control group. This was opposed by the mu opioid antagonist naloxone (1 or 2 mg/kg) in a dose-dependent manner. 3. To determine whether these effects were operative in the brain, rats received an injection of either morphine 50 micrograms/kg or its diluent (control) into the lateral cerebral ventricle intracerebroventricularly (i.c.v.). Morphine significantly increased (P < 0.05) the threshold for the development of arrhythmias. 4. To further explore whether this effect was operative at the mu opioid receptor, a more specific mu opioid receptor agonist morphiceptin (50 micrograms/kg) was administered i.c.v. and produced a significant increase (P < 0.05) in the threshold for cardiac arrhythmias compared with controls. 5. The action of morphine was further established to be operating through mu opioid receptors from experiments with the i.c.v. administration of naloxone (+) and naloxone (-) followed by morphine showing that the action of morphine in the brain was prevented by the opioid antagonist naloxone but not by its stereo-isomer that is not a mu opioid receptor antagonist. 6. These data suggest a role for morphine to modulate cardiac arrhythmias, specifically to increase arrhythmia threshold, through an action within the CNS at mu opioid receptors.
Rabkin
S W
SW
Research Center, University Hospital, University of British Columbia, Vancouver, Canada.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects*; D004723:Endorphins / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000037:antagonists & inhibitors*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D004723:Endorphins; D017450:Receptors, Opioid, mu; D009020:Morphine; C028889:morphiceptin; D004837:Epinephrine