VENTILATION IN MORPHINE-MAINTAINED RHESUS-MONKEYS .1. 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 pres ence of normal air to 36 +/- 1 breaths/min, from a baseline rate of 25 +/- 1 breaths/min. Naltrexone did not affect other measures of ventil ation 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 ventilat ory rate in the presence of normal air to 52 +/- 4 breaths/min. Naltre xone also dose-dependently increased ventilatory rate in the presence of 3% and 5% CO2; tidal volume was not affected by naltrexone administ ration. Doubling the maintenance dose of morphine to 6.4 mg/kg/day fur ther increased the ventilatory effects of naltrexone. Withholding the maintenance dose of morphine also increased ventilatory rate without a ffecting tidal volumes, in a manner similar to that seen after naltrex one administration. These results are consistent with the view that ch anges in ventilation can be used to measure precipitated and abstinenc e-associated opioid withdrawal in monkeys.