EFFECTS OF MET-ENKEPHALIN ON GABAERGIC SPONTANEOUS MINIATURE IPSPS INORGANOTYPIC SLICE CULTURES OF THE RAT HIPPOCAMPUS

The action of met-enkephalin on GABAergic spontaneous miniature IPSPs (smIPSPs) was investigated in CA1 neurons from hippocampal slice cultu res. In the presence of excitatory amino acid blockers ihydroxy-6-nitr o-7-sulphamoyl-benzo(F)quinoxaline, DL-2-amino-5-phosphonovaleric acid ) and TTX, a continuous high-frequency bombardment of smIPSPs was reco rded. The smIPSPs were blocked by the GABA(A) antagonist bicuculline. The occurrence of the smIPSPs was random and their amplitude distribut ion was skewed toward larger smIPSPs. Met-enkephalin (10-20 mum) rever sibly reduced the frequency and changed the amplitude distribution of the smIPSPs. The proportion of ''large'' smIPSPs was reduced, but a lo ss of ''small'' smIPSPs also contributed to the reduction in smIPSP fr equency. The selective mu-receptor agonist DAGO mimicked the effect of met-enkephalin and naloxone blocked the effect of DAGO. Hyperpolariza tion of the neuronal membranes, produced by reducing the extracellular K+ concentration, did not reduce the frequency of the smIPSPs, nor di d it block the effect of DAGO. Reduction of the extracellular concentr ation of Ca2+ combined with an increase in extracellular Mg2+ or the a ddition of Cd2+ did not reduce the smIPSP frequency, nor did it block the effect of DAGO. These results suggest that CA1 pyramidal cells of hippocampal organotypic cultures are tonically inhibited by spontaneou s release of GABA, through a release mechanism that is independent of propagated sodium action potentials. Met-enkephalin and DAGO reduce th e tonic inhibition by reducing the frequency of the smIPSPs, through a direct action on the presynaptic GABAergic terminals. The effect was probably not mediated by hyperpolarization of the presynaptic membrane or by modulation of presynaptic Ca2+ currents.