PT  - JOURNAL ARTICLE
AU  - Paronis, Carol A.
AU  - Woods, James H.
TI  - Ventilation in Morphine-Maintained Rhesus Monkeys. I: Effects of Naltrexone and Abstinence-Associated Withdrawal
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DP  - 1997 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 348--354
VI  - 282
IP  - 1
4099  - http://jpet.aspetjournals.org/content/282/1/348.short
4100  - http://jpet.aspetjournals.org/content/282/1/348.full
SO  - J Pharmacol Exp Ther1997 Jul 01; 282
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics