Hypersensitivity of morphine-tolerant rabbits to the respiratory stimulant effect of a cholinergic agonist

J Pharmacol Exp Ther. 1983 Jul;226(1):232-7.

Abstract

The effect of morphine and oxotremorine, a centrally acting cholinergic agonist on the respiratory rate and arterial blood gases, was studied in rabbits given saline, increasing doses of morphine (5 mg/kg, 2 days; 10 mg/kg, 2 days; and 20 mg/kg, 3 days) injected at 12-hr intervals for 1 week. Care was taken to ensure that the chronically morphine-treated rabbits were neither under the influence of a previous dose of morphine nor in a phase of withdrawal when the response to test doses was measured. Tolerance to the respiratory depressant effect of morphine was demonstrated by the finding that a 5 times greater dose of morphine was needed to decrease respiration rate and raise arteriolar pCO2 than that given to saline-treated rabbits. The respiratory stimulant effect of oxotremorine, as demonstrated by an increase in respiration rate and decrease in PaCO2, was significantly greater in morphine-tolerant rabbits. It is concluded that chronic opiate treatment can induce supersensitivity of the cholinergic systems subserving control of respiration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Dioxide / blood
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Tolerance
  • Kinetics
  • Male
  • Morphine / pharmacology*
  • Oxotremorine / pharmacology*
  • Rabbits
  • Respiration / drug effects*

Substances

  • Carbon Dioxide
  • Oxotremorine
  • Morphine