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Paronis CA, Woods JH. 
“Ventilation in morphine-maintained rhesus monkeys I: Effects of naltrexone and abstinence-associated withdrawal”. 
J Pharmacol Exp Ther. 1997 Jul 07;282(1):348-54.
Abstract
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.
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