Enhanced sensitivity to the antinociceptive effects of kappa opioids in naltrexone-treated rats: dose- and time-dependent effects.

The purpose of the present study was to examine sensitivity to the antinociceptive effects of kappa opioids during chronic treatment with the nonselective opioid antagonist naltrexone. In a warm-water tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from water maintained at 50 and 55 degrees C were recorded. Prior to chronic treatment, spiradoline, U50,488 and (-)-pentazocine produced dose-dependent increases in tail-withdrawal latencies at both 50 and 55 degrees C. Chronic treatment with 3.0 mg/kg naltrexone twice daily (b.i.d.) failed to alter sensitivity to the antinociceptive effects of spiradoline when tested 24 h following naltrexone administration. When the maintenance dose of naltrexone was increased to 30 mg/kg b.i.d., sensitivity to the effects of spiradoline was reduced when tested 24 h after naltrexone administration, but enhanced when tested 48 h after naltrexone administration. Enhanced sensitivity was also observed to the antinociceptive effects of U50,488 and (-)-pentazocine when tested 48 h after chronic treatment with 30 mg/kg naltrexone. After termination of chronic treatment, sensitivity to the antinociceptive effects of spiradoline, U50,488 and (-)-pentazocine returned to that originally observed prior to naltrexone treatment. These data indicate that chronic naltrexone treatment enhances sensitivity to the antinociceptive effects of kappa opioids, and that this effect is both dose and time dependent.