Antinociceptive effects of cocaine in rhesus monkeys

The antinociceptive effects of (-)cocaine, (+)cocaine, and cocaine methiodide administered alone and in combination with the mu-opioid agonist morphine were evaluated in rhesus monkeys. The shaved tails of four rhesus monkeys were exposed to warm water (42, 46, 50, and 54 degrees C), and tail-withdrawal latencies (20-s maximum) from each temperature were determined. (-)Cocaine (0.032-1.8 mg/kg, s.c.) produced dose-dependent antinociceptive effects and enhanced the antinociceptive effects of morphine. Neither (+)cocaine nor cocaine methiodide (0.1-10 mg/kg, s.c.) produced antinociception or altered the effects of morphine. Pretreatment with the serotonin receptor antagonist mianserin (0.1-04).32 mg/kg, i.m.) produced dose-dependent rightward shifts in the dose-effect curve for (-)cocaine alone, and attenuated (-)cocaine-induced enhancement of the antinociceptive effects of morphine. However, mianserin (0.32 mg/kg, i.m.) did not alter the antinociceptive effects of morphine alone. These results suggest that in rhesus monkeys, the effects of cocaine on nociception may be stereoselective and centrally mediated. These findings further suggest that the antinociceptive effects of cocaine in primates may be mediated at least in part by cocaine's effects on serotonergic systems.