In vivo and in vitro epileptogenic effects of the enkephalinergic system

The relationships between the in vivo epileptogenic effects of opiates and the in vitro electrophysiological activity of opiates, enkephalins and inhibitors of endogenous peptidase were analyzed in order to ascertain the effective functional role of the endogenous opiate peptidergic system in the control of neuronal excitability. Morphine, enkephalins and related drugs induced in rats and rabbits naloxone-sensitive non-convulsive hippocampal EEG epileptiform activity after systemic or central administration. Higher doses of morphine and related drugs induced naloxone-insensitive convulsive EEG epileptiform activity within all the brain after systemic or central administration. Morphine and enkephalins, selectively acting at mu opiate receptors (DAGO, morphiceptin), increased in rat hippocampal slices the excitability of CA1 pyramidal cells, an effects revealed by a naloxone-sensitive increase of the magnitude of the CA1 population spike and by the appearance of several additional epileptiform population spikes. Enkephalins, selectively acting at delta opiate receptors (DPDPE, deltorphin), produced a naloxone-sensitive increase of the magnitude of the CA1 population spike but failed to induce the appearance of several additional epileptiform population spikes. Enkephalinase inhibitors (thiorphan, SCH32615) failed to affect the basal CA1 electrical response, but potential the epileptiform activity induced by DAGO. Collectively, the data indicate that hippocampal mu opiate receptors mediate the excitatory-epileptogenic effects of opiates.