Differential effects of selective mu-, kappa- and delta-opioid antagonists on electroshock seizure threshold in mice

The effects of the selective opioid antagonists cyprodime (mu; 1, 3, 10, 30 mg/kg IP), norbinaltorphimine (kappa; 3, 10, 30 mg/kg IP) and naltrindole (delta; 0.3, 1, 3, 10 mg/kg IP) on electroshock seizure threshold in mice were compared with those of the universal opioid antagonist naloxone (0.3, 1, 10 mg/kg IP). Seizure threshold was increased by mu-receptor blocking doses of both cyprodime and naloxone, unaltered by norbinaltorphimine and decreased (in a dose-related manner) by all doses of naltrindole. The effects of naltrindole were similar to those of the established pro-convulsant agent bicuculline (1 mg/kg IP); however, naloxone and cyprodime produced relatively small increases in seizure threshold when compared with phenytoin (doses up to 30 mg/kg IP). The differential effects of mu-, kappa- and delta-receptor antagonists obtained in this study suggest that electroshock seizure threshold in mice may be controlled, at least in part, by a balance between endogenous opioids acting either pro-convulsantly through mu-receptors or anti-convulsantly via delta-receptors.