Electrophysiological effects of selective opioid agonists on spontaneous and evoked neuronal activity in the dentate gyrus of the hippocampus in vivo.

The mechanism by which endogenous opioid peptides regulate neuronal excitability in the dentate gyrus of the hippocampus remains unclear. We studied the neurophysiologic responses to various receptor-selective opioids, given both iontophoretically and systemically, in anesthetized rats. Single unit action potentials and field potential recordings were taken from electrophysiologically classified dentate granule cells (DGCs) or dentate interneurons (INTs). The mu receptor agonist ([D-Ala2, NMe-Phe4, Gly-ol]-Enkephalin (DAMGO)) increased the responsiveness of DGCs to perforant path stimulation, although it did not induce spontaneous activity in DGCs. We did not see this facilitation with systemic morphine sulfate (MS). However, both DAMGO and MS produced similar, primarily inhibitory, effects on INTs. The responsiveness of an individual INT tended to be related to the cell's location in the dentate gyrus, and to a lesser degree, to its baseline spontaneous discharge frequency. U-50488H, a selective kappa receptor agonist, had little effect on either DGCs or INTs. Our results suggest that mu selective opioids have a complex neuropharmacology in this region involving interaction among different types of INTs to produce an effect on the principal output cells.