Opioid-mediated facilitation of long-term potentiation at the lateral perforant path-dentate granule cell synapse

Opioid effects on the development of long-term potentiation (LTP) were investigated at the lateral perforant path (LPP)-dentate granule cell synapse of the hippocampal slice. High frequency stimuli were delivered to the outer molecular layer of the dentate to tetanize the LPP. Significant LTP was induced in the amplitude of the orthodromic population spike and the slope of the population excitatory postsynaptic potential recorded from the granule cell layer and molecular layer. Bath application of naloxone (0.1-10 microM), an opioid antagonist, induced a dose-dependent reduction in the potentiation of both orthodromic population spike and excitatory postsynaptic potential evoked in the LPP, but not in adjacent medial perforant path. PLO17 ([N-MePhe3-D-Pro4]morphiception; 0.3 or 1 microM), a mu opioid agonist, reduced the threshold for LTP and increased the amount of LTP in the LPP. PLO17 also reduced recurrent inhibition and enhanced an N-methyl-D-aspartate (NMDA) receptor-mediated component in single pulse-evoked field potentials in the LPP. The effects of PLO17 were antagonized by 1 microM naloxone and the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (100 microM). These findings suggest that endogenous opioids released during high frequency stimulation play an important role in the induction of LTP at the LPP synapses. A mu receptor-mediated disinhibition which increases current flow through NMDA channels may contribute to the opioid enhancement of LTP in the dentate gyrus.