Convulsant and anticonvulsant effects of opioids: relationship to GABA-mediated transmission.

The convulsant benzodiazepine Ro 5-3663, bicuculline and picrotoxin induced electroencephalographic (EEG) and behavioural convulsions. In rabbits, the EEG modifications consisted, with increasing doses, of three different patterns: slow waves in the optic lead, spike- and wave-complexes in the sensorimotor cortex, and grand-mal generalized seizures. These EEG effects were terminated by administration of diazepam (1 mg/kg) and morphine (0.25-1.0 mg/kg). Naloxone, in doses of 5-10 mg/kg, potentiated the effects of the three convulsant drugs. This potentiating phenomenon was also antagonized by the administration of diazepam and morphine. In membrane preparations, obtained from rat cortex, deprived of endogenous modulators of [3H]GABA binding, naloxone but not morphine, was able to inhibit [3H]GABA binding to its specific recognition sites. These data agree with previous findings indicating a GABA-antagonistic effect of naloxone, and support the hypothesis that the anticonvulsant effect of morphine might be, at least in part, due to an increase in GABAergic activity at the synaptic level.