Opioid-mediated facilitation of long-term depression in rat hippocampus

Previous studies have demonstrated that opioid substances are often inhibit ors of the gamma -aminobutyric acid (GABA) transmitter system in the hippoc ampal formation, and that GABA-mediated inhibition is a potent modulator of synaptic plasticity. Field excitatory postsynaptic potentials were recorde d from the CA1 region of rat hippocampal slices in response to stimulation of the Schaffer collateral fibers to monitor the effects of acute opioid ex posure on the induction of long-term depression (LTD) at excitatory synapse s in the stratum radiatum. Exogenous application of a selective mu -opioid agonist resulted in a greater than 2-fold enhancement of LTD, whereas kappa - and delta -agonists did not significantly affect LTD magnitude. Costimula tion of the opioid peptide-containing stratum lacunosum-moleculare during L TD induction also resulted in a facilitation of LTD in the stratum radiatum , an effect prevented by prior administration of an opioid antagonist. Thes e results suggest that both exogenously applied and endogenously released o pioids can act to facilitate LTD of the Schaffer collateral input to CA1 py ramidal neurons.