Ventilation in morphine-maintained rhesus monkeys. I: Effects of naltrexone and abstinence-associated withdrawal.
The effects of naltrexone on ventilation were examined in three rhesus monkeys maintained on 3.2 mg/kg/day morphine. Before the onset of the daily morphine-dosing regimen, naltrexone had only modest effects on ventilation; a dose of 32 mg/kg increased ventilatory rate in the presence of normal air to 36 +/- 1 breaths/min, from a baseline rate of 25 +/- 1 breaths/min. Naltrexone did not affect other measures of ventilation in the presence of normal air or 5% CO2. Subsequent to the onset of the daily morphine injection regimen, naltrexone dose-dependently increased ventilatory rate at doses 4 orders of magnitude lower (0.001-0.01 mg/kg) than those effective in nondependent monkeys. A dose of 0.01 mg/kg naltrexone in morphine-maintained monkeys increased ventilatory rate in the presence of normal air to 52 +/- 4 breaths/min. Naltrexone also dose-dependently increased ventilatory rate in the presence of 3% and 5% CO2; tidal volume was not affected by naltrexone administration. Doubling the maintenance dose of morphine to 6.4 mg/ kg/day further increased the ventilatory effects of naltrexone. Withholding the maintenance dose of morphine also increased ventilatory rate without affecting tidal volumes, in a manner similar to that seen after naltrexone administration. These results are consistent with the view that changes in ventilation can be used to measure precipitated and abstinence-associated opioid withdrawal in monkeys.
Paronis
C A
CA
Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, USA.
Woods
J H
JH
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D009294:Narcotics; D009271:Naltrexone; D009020:Morphine