Studies on the excitatory and inhibitory influence of intracerebroventricularly injected opioids on seizure thresholds in rats.

The influence of centrally administered meperidine, normeperidine and pentazocine on the excitability of brain was studied by measuring the threshold for flurothyl-induced convulsions in rats. All three opioids are reported to lower seizure thresholds when given subcutaneously to rats in this test. Dose-and time-dependent changes in the seizure threshold occurred after intracerebroventricular injection of pentazocine (10-160 micrograms), meperidine (25-150 micrograms) and normeperidine (50-150 micrograms). Rapid increases in the seizure threshold were associated with pentazocine and meperidine, whereas a slowly developing decrease in the threshold was caused by normeperidine. Naloxone (10 mg/kg, s.c.) antagonized the anticonvulsant effect of meperidine (but not that of pentazocine) and enhanced the proconvulsant effect of normeperidine. Thebaine (25-150 micrograms), which had no marked influence on the seizure threshold when given intracerebroventricularly, lowered the threshold after subcutaneous injection of 12.5 and 25 mg/kg. This effect was not altered by injection of naloxone. These results show that centrally administered opioids can act on excitatory or inhibitory systems that regulate seizure mechanisms in the rat brain. Furthermore both naloxone-sensitive and naloxone-insensitive components are involved. Meperidine, pentazocine and thebaine have different actions on the seizure threshold after intracerebroventricular, as opposed to subcutaneous, administration. This work has, therefore, identified the route of administration as a critical variable in the effect of opioids on the seizure threshold in rats.