Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo.

The role of opioid receptors in long-term potentiation (LTP) of the medial (MPP) and lateral (LPP) divisions of the perforant path-granule cell projection was investigated in urethane anesthetized rats. A stimulating electrode was positioned in the dorsomedial or ventrolateral aspect of the angular bundle for selective activation of the MPP and LPP, respectively. A push-pull cannula served to focally perfuse artificial cerebrospinal fluid (ACSF) across the perforant path terminal zone, while perforant path evoked potentials were monitored in the dentate hilus. Robust LTP of the excitatory postsynaptic potential (EPSP) initial slope and population spike height was induced by high frequency stimulation (400 Hz, 8 bursts of 8 pulses) applied to the medial or lateral perforant path in rats perfused with standard medium. In the lateral perforant path, a putative proenkephalin system, LTP of the EPSP and population spike was blocked when ACSF containing 100 microM of the opioid receptor antagonist naloxone was present during the tetanus, while perfusion with 0.1 microM naloxone prevented EPSP potentiation but only reduced the magnitude of the population spike increase. Naloxone had no effect on LTP induction in the MPP. Importantly, 0.1 microM ICI 174,864, a selective antagonist of delta opioid receptors, blocked LTP of synaptic transmission in the LPP while leaving the population spike increase intact. The results indicate that LTP of synaptic transmission in the LPP requires activation of delta opioid receptors, while 'non-delta' opioid receptors may be involved in augmenting granule cell output. This opioid receptor-dependent LTP illustrates peptidergic regulation of synaptic plasticity in the hippocampus.