Influence of tolerance to and physical dependence on opioid analgesics on cortical evoked potential in rats.

The influence of single and repeated doses of morphine, pentazocine, and chlorpromazine on the latent time of cortical evoked potentials was observed in rats. The evoked potentials were induced by electrical stimulation of the sciatic nerve under the condition of curarization and artificial respiration. The evoked potential consisted of 4 phases. The latent time of the N2 component was prolonged by single dose administration of morphine at 5 mg/kg, s.c., pentazocine at 15 mg/kg, s.c., or chlorpromazine at 2 mg/kg, s.c. The effects of morphine and pentazocine were antagonized by naloxone but that of chlorpromazine was not. By repeated administration of morphine at 5 mg/kg or pentazocine at 15 mg/kg twice daily for 4 weeks, the prolongation of latent time tended to disappear gradually. Further, in these rats the latent time became shorter than that of normal rats after naloxone administration or natural withdrawal for 18 hr. Thus the development of tolerance to and physical dependence on these drugs were demonstrated by recovering and shortening of the latent time, even when withdrawal signs were not apparently observed in the rats' gross behavior. On the other hand, repeated administration of chlorpromazine at 2 mg/kg twice daily for 4 weeks did not produce such shortening of the latent time as was observed with morphine and pentazocine. These results indicate that the evoked potential can serve as a sensitive parameter for observation of the development of tolerance to and physical dependence on opioid analgesics in rats.