Abstract
Previous studies have demonstrated that opioid substances are often inhibitors of the γ-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 κ- and δ-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.
Footnotes
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Send reprint requests to: Dr. John J. Wagner, College of Pharmacy, 123 Sudro Hall, Fargo, ND 58105. E-mail:johnwagn{at}prairie.nodak.edu
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J.J.W. was funded by National Institute on Drug Abuse (DA09603 and DA11040), L.R.E. was funded by the Merck Research Scholar Program, and A.M.T. was funded in part by the Neuropsychiatric Research Institute.
- Abbreviations:
- GABA
- γ-aminobutyric acid
- LTP
- long-term potentiation
- LTD
- long-term depression
- LFS
- low-frequency stimulation
- NMDA
- N-methyl-d-aspartate
- s. radiatum
- stratum radiatum
- s. lac-mol.
- stratum lacunosum-moleculare
- fEPSP
- field excitatory postsynaptic potential
- SC
- Schaffer collateral
- DAMGO
- [d-ala2,N-Me-Phe4,Gly5-ol]-enkephalin
- TA
- temporoammonic
- NMDAR
- NMDA receptor
- APV
- dl-2-amino-5-phosphonovaleric acid
- Received September 19, 2000.
- Accepted October 30, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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