Electrophysiological effects of dynorphin peptides on hippocampal pyramidal cells in rat

Single-unit extracellular recording was carried out in rats to characterize the effects of dynorphin and several structurally related peptides on hippocampal pyramidal cell activity. Dynorphin, applied electrophoretically or by pneumatic pressure, produced a dose-dependent depression of both spontaneous and glutamate-evoked discharge in a majority (63%) of CA1 and CA3 cells tested. In addition, a small number of cells in both cellular fields responded to the peptide with a prolonged elevation in firing. The inhibitory effects of dynorphin were not blocked by naloxone. Moreover, administration of des-tyrosine-dynorphin depressed the firing of pyramidal cells in a manner similar to that of the parent compound. Ethylketocyclazocine produced a mixed pattern of excitatory and inhibitory effects, whereas naloxone-sensitive elevations in firing were most often observed with the application of dynorphin-(1-8). Application of [Leu5]enkephalin produced only facilitations in pyramidal cell firing. The possibility is raised that biologically significant non-opiate actions, in addition to potent opiate-mediated effects, may occur upon release of pro-dynorphin peptides in the hippocampus.