Abstract

Both mu and delta opioid receptors are abundant in the dentate gyrus of the hippocampus and proenkephalin-derived peptides are present in the perforant path fibers. Intracellular recordings were made from dentate granule cells in rat hippocampal slices; neurons were identified as granule cells by biocytin injection and subsequent histological examination. Opioids selective for either mu receptors ([D-Ala2,MePhe4,Gly5]enkephalin-ol) or delta receptors ([D-Pen2,5]enkephalin) and [Met5]enkephalin hyperpolarized most granule cells. The hyperpolarization by [Met5]enkephalin was potentiated by the enkephalinase and aminopeptidase inhibitors thiorphan and bestatin and blocked by antagonists selective for either mu receptors ([Cys2,Tyr3,Orn5,Pen7]somatostatinamide) or delta receptors (N,N-bisallyl-Tyr-(aminoisobutyrate)2-Phe-Leu-OH). Synaptic potentials mediated by gamma-aminobutyric acid (GABA) acting at GABAA receptors (blocked by bicuculline) or GABAB receptors (blocked by 2-hydroxysaclofen) were reduced by [Met5]enkephalin, [D-Ala2,MePhe4,Gly5]enkephalin-ol and [D-Pen2,5]enkephalin. Synaptic potentials mediated by excitatory amino acids (blocked by 6-cyano-7-nitroquinoxaline-2,3-dione and 2-amino-5-phosphonovaleric acid) were evoked by stimulation of the perforant path in the subiculum; opioids slightly reduced the amplitude of the initial peak and sometimes caused the appearance of one or more later components. It was concluded that the opioids selective for mu and delta receptors directly hyperpolarize granule cells and also inhibit GABAA and GABAB synaptic potentials.