Vol. 282, Issue 1, 348-354, 1997

Ventilation in Morphine-Maintained Rhesus Monkeys. I: Effects of Naltrexone and Abstinence-Associated Withdrawal^1,2

Carol A. Paronis and James H. Woods

Departments of Pharmacology (C.A.P., J.H.W.) and Psychology (J.H.W.), The University of Michigan Medical School, Ann Arbor, Michigan

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.