Electrophysiological interactions of enkephalins with neuronal circuitry in the rat hippocampus. I. Effects on pyramidal cell activity.

Effects of enkephalins on hippocampal pyramidal cell activity were studied in situ and in the in vitro hippocampal slice. Active enkephalin derivatives produced a dose-dependent naloxone-reversible excitation in both preparations whereas inactive enkephalin derivatives had no effect. Several different types of experiments, carried out in the slice, strongly suggest that this excitation is due to blockade of inhibitory pathways. First, when the pyramidal cell population spike is increased during enkephalin administration, no change is seen in the simultaneously recorded EPSP. Second, the magnitude of the enkephalin effect is highly correlated with the amount of inhibition, as judged by paired-pulse stimulation, initially present in the slice. Third, if inhibitory pathways are depressed by a brief period of hypoxia, enkephalin has little effect. Finally, enkephalin responses are mimicked by picrotoxin, which selectively antagonizes inhibitory input to the pyramidal neuron. Since enkephalins do not block the effects of GABA, the putative inhibitory transmitter, these data suggest that opioid peptides depress the inhibitory interneurons and disinhibit the pyramidal cells.