Peripheral versus central cardiorespiratory effects of morphine

Neuropharmacology. 1982 Oct;21(10):1019-26. doi: 10.1016/0028-3908(82)90116-2.


The administration of morphine sulfate (MS, 2 mg/kg) into the right atrium in decerebrate rats, produced a dramatic bradycardia, apnea, and a slight transient biphasic blood pressure response within 1 sec. The bradycardia was slowly restored to control levels within 8-10 min and was prevented by pretreatment with atropine. Apnea (7.3 +/- 2.2 sec) was followed by a period of rapid shallow breathing. Acute tolerance to these effects developed to subsequent doses of morphine. In paralyzed artificially ventilated animals, morphine produced: (1) cessation of phrenic nerve (PN) activity which was followed by bursts of shortened duration; and (2) concomitant excitation of the recurrent laryngeal nerve (RLN), this activity exhibited a continuous discharge which was asynchronous with that of phrenic nerve. These actions of morphine were qualitatively similar to those observed with phenyldiguanide (PDG) and were found to be reflexogenic, i.e. emanating from the lungs via stimulation of pulmonary C-fibers. Bilaterally vagotomized animals only responded to morphine with respiratory depression, characterized by a severe decrease in respiratory rate and minute ventilation. On the other hand, animals with intact vagi showed stimulation of rate and minute ventilation following a brief period of apnea. They were less sensitive than vagotomized animals to the depressant action during the first 8 min after administration of morphine. All the effects of morphine were blocked by pretreatment with naloxone (50-400 micrograms/kg, i.v.). These results indicate that the initial cardiorespiratory effects of morphine are due to a peripheral reflex action arising from the stimulation of opiate receptors associated with pulmonary C-fibers, e.g. J-fibers.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects*
  • Cardiovascular System / drug effects*
  • Heart Rate / drug effects
  • Lung / innervation
  • Male
  • Morphine / pharmacology*
  • Peripheral Nerves / drug effects*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Opioid / drug effects
  • Reflex / drug effects
  • Respiration / drug effects*
  • Vagus Nerve / physiology


  • Receptors, Opioid
  • Morphine