ANTINOCICEPTIVE EFFECTS OF COCAINE OPIOID COMBINATIONS IN RHESUS-MONKEYS/

This study characterized the antinociceptive effects of cocaine alone and in combination with mu, delta, and kappa opioids in rhesus monkeys . The shaved tails of four rhesus monkeys were exposed to warm water ( 42, 46, 50, 54, and 58 degrees C), and tail withdrawal lactencies (20 sec maximum) from each temperature were determined. The temperature th at produced a tail withdrawal latency of 10 sec (T10) was interpolated , and drug-induced changes in the T10 value (Delta T10) were calculate d. Dose-dependent increases in Delta T10 were produced by cocaine (0.0 32-1.8 mg/kg), the high efficacy mu agonist fentanyl (0.001-0.1 mg/kg) , the intermediate efficacy mu agonist morphine (0.1-18 mg/kg), the lo w efficacy mu agonist nalbuphine (1-32 mg/kg), and the kappa agonist U 69,593 (0.0032-0.1 mg/ kg). The delta agonist BW373U86 (0.56 mg/kg) pr oduced no effect. Relative maximum effects, determined from the maximu m Delta T10 values produced by each drug, were fentanyl greater than o r equal to rolidinyl)1-oxaspiro[4,5]dec-8-yl]benzeneacetamide > morphi ne > nalbuphine > cocaine > BW373U86. When individual doses of cocaine (0.1-1.8 mg/kg) and morphine (0.32-10.0 mg/kg) were combined, cocaine produced a dose-dependent increase in the effects of each dose of mor phine, and the antinociceptive effects of most cocaine/ morphine combi nations were significantly greater than the antinociceptive effects of either cocaine or morphine alone. Cocaine (1.8 mg/kg) was also combin ed with nalbuphine (1.0, 10 mg/kg), fentanyl (0.001, 0.032 mg/kg), BW3 73U86 (0.56 mg/kg) and U69,593 (0.0032-0.056 mg/kg). Cocaine/nalbuphin e combinations produced effects markedly greater than either drug alon e. Cocaine in combination with a low dose of fentanyl (0.001 mg/kg) pr oduced effects equivalent to cocaine alone, whereas cocaine in combina tion with a high dose of fentanyl (0.032 mg/kg) produced effects equiv alent to fentanyl alone. The cocaine/BW373U86 combination produced eff ects identical to cocaine alone. Cocaine/U69,593 combinations produced little or no antinociception, and 1.8 mg/kg cocaine in combination wi th the highest dose of U69,593 (0.056 mg/kg) produced significantly le ss antinociceptive effect than either cocaine or U69,593 alone. These findings suggest that, in rhesus monkeys, cocaine enhances the antinoc iceptive effects of low to medium efficacy mu agonists but not high ef ficacy mu agonists or BW373U86. In contrast, cocaine and kappa agonist s can attenuate each other's antinociceptive effects.