Modulation of cocaine-induced antinociception by opioid-receptor agonists

Cocaine can produce antinociception in a number of animal models. The present experiments were designed to determine if opioid receptor agonists modulate cocaine-induced antinociception in rats. Cocaine produced a dose-dependent increase in antinociception in the hot-plate, but not paw-pressure, test. The combination of cocaine and morphine or [D-Pen2, D-Pen5]enkephalin (DPDPE) produced results no greater than simple additivity in the hot-plate test. However, the combination of cocaine and morphine produced greater antinociception than morphine alone in the paw-pressure test. A low dose of U69,593 potentiated the effects of cocaine in the hot-plate test. In contrast, cocaine attenuated the effect of U69,593 in the paw-pressure test. Both naltrexone and the selective kappa-opioid receptor antagonist nor-binaltorphamine (nor-BNI) blocked the potentiation of cocaine-induced antinociception by U69,593. The combination of U69,593 and cocaine can produce superadditive or subadditive effects, depending upon the doses and antinociceptive assay used.