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Pharmacology. 1987;35(6):317-26.

Role of endogenous opioids on ventilation and chemical control of breathing in pentobarbitone-anesthetized rats.

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  • 1Department of Allergy and Inflammation, Schering-Plough Corporation, Bloomfield, N.J.

Abstract

To investigate the role of endogenous opioids on ventilatory control in pentobarbitone-anesthetized rats, the opioid antagonists naloxone and naltrexone were studied for their effects on ventilation, arterial blood gases and on ventilatory responses to hypoxia and carbon dioxide. In animals breathing room air, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) caused a dose-related increase in tidal volume, respiratory rate and minute volume. These ventilatory responses were rapid in onset and were associated with a decrease in arterial PaCO2, an increase in arterial pH and an increase in arterial PaO2. Intravenous naloxone (4 mg/kg) antagonized the increase in PaCO2 and decrease in arterial pH induced by the administration of morphine (3 mg/kg, i.v.). In animals breathing 100% O2, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) did not stimulate ventilation. Furthermore, intracerebroventricular administration of naloxone (15 and 150 micrograms) had no measurable effect on ventilation. Ventilatory responses to both hypoxia and carbon dioxide were not augmented by intravenous naloxone (4 mg/kg) and naltrexone (4 and 10 mg/kg). In fact, the increase in respiratory rate due to hypoxia was significantly (p less than 0.05) reduced by naltrexone (10 mg/kg, i.v.). In conclusion, our results demonstrate that naloxone and naltrexone caused hyperventilation in pentobarbitone-anesthetized rats. This effect was probably triggered by stimulation of the peripheral arterial chemoreceptors and did not involve mechanisms directly associated with the central nervous system. However, endogenous opioids were not involved in the chemical control of breathing in pentobarbitone-anesthetized rats since ventilatory responses to hypoxia and carbon dioxide were not changed by administration of these opioid antagonists.

PMID:
3124142
[PubMed - indexed for MEDLINE]
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