Effects of mu-opioid receptor modulation on GABAB receptor synaptic function in hippocampal CA1.

Activation of mu-opioid receptors (MORs) alters information coding, synaptic plasticity, and spatial memory in hippocampal CA1. In CA1, MORs act by inhibiting GABA release onto both GABA(A) and GABA(B) receptors exclusively. MOR activation can facilitate excitatory inputs in CA1 dendritic layers by inhibiting synaptic activation of GABA(A) receptors. In this study, we use voltage-sensitive dye imaging to show that MOR activation by the MOR agonist DAMGO suppressed GABA(B) inhibitory postsynaptic potentials in all layers of CA1. When stimulating excitatory input in stratum oriens (SO), stratum radiatum (SR), or stratum lacunosum-moleculare (SLM) with five pulses at 20 Hz in the presence of bicuculline (50 microM), DAMGO (1 muM) was most effective at increasing the amplitude of the last excitatory event. This effect was reversed by the MOR antagonist CTOP (1 muM) and occluded by the GABA(B) receptor agonist CGP 55845 (10 microM). DAMGO was less effective at increasing the amplitude of later excitatory events compared with the effect of CGP 55845. DAMGO was relatively ineffective at increasing the amplitude of excitatory inputs in SLM but had significantly greater effects on excitatory events as they propagated to stratum pyramidale (SP). When stimulating in SR, DAMGO was least effective at increasing excitatory amplitudes in SLM and most effective in SP and SO. Finally, DAMGO was equally effective at increasing excitatory activity amplitudes in all layers of CA1 after stimulating in SO. Therefore MOR suppresses GABA(B) synaptic hyperpolarizations in all layers of CA1 and most effectively facilitates excitatory activity in CA1 output layers.