Vol. 296, Issue 3, 776-781, March 2001

Opioid-Mediated Facilitation of Long-Term Depression in Rat Hippocampus

John J. Wagner, Lida R. Etemad and Angela M. Thompson

Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo, North Dakota

Previous studies have demonstrated that opioid substances are often inhibitors of the -aminobutyric acid (GABA) transmitter system in the hippocampal formation, and that GABA-mediated inhibition is a potent modulator of synaptic plasticity. Field excitatory postsynaptic potentials were recorded from the CA1 region of rat hippocampal slices in response to stimulation of the Schaffer collateral fibers to monitor the effects of acute opioid exposure on the induction of long-term depression (LTD) at excitatory synapses in the stratum radiatum. Exogenous application of a selective µ-opioid agonist resulted in a greater than 2-fold enhancement of LTD, whereas - and -agonists did not significantly affect LTD magnitude. Costimulation of the opioid peptide-containing stratum lacunosum-moleculare during LTD induction also resulted in a facilitation of LTD in the stratum radiatum, an effect prevented by prior administration of an opioid antagonist. These results suggest that both exogenously applied and endogenously released opioids can act to facilitate LTD of the Schaffer collateral input to CA1 pyramidal neurons.