ACTIONS OF THE ORL(1) RECEPTOR-LIGAND NOCICEPTIN ON MEMBRANE-PROPERTIES OF RAT PERIAQUEDUCTAL GRAY NEURONS IN-VITRO

The actions of the endogenous ORL(1)-receptor ligand nociceptin on the membrane properties and synaptic currents in rat periaqueductal gray (FAG) neurons were examined by the use of whole-cell patch-clamp recor ding in brain slices. Nociceptin produced an outward current in all ne urons tested, with an EC(50) of 39 +/- 7 nM. The outward current was u naffected by naloxone. Outward currents reversed polarity at -110 +/- 3 mV in 2.5 mM extracellular potassium, and the reversal potential inc reased when the extracellular potassium concentration was raised (slop e 66.3 mV/log[K+](o) mM). Thus, the nociceptin-induced outward current was attributable to an increased K+ conductance. Nociceptin inhibited evoked fast GABAergic (IPSCs) and glutamatergic (EPSCs) postsynaptic currents and increased paired-pulse facilitation in a subpopulation of PAG neurons. Nociceptin inhibited evoked IPSCs and EPSCs in similar t o 50% of neurons throughout the PAG, except in the ventrolateral PAG, where nociceptin inhibited evoked IPSCs in most neurons. Nociceptin de creased the frequency of spontaneous miniature postsynaptic currents ( mIPSCs and mEPSCs) in a subpopulation of PAG neurons but had no effect on their amplitude distributions. Thus, nociceptin had a presynaptic inhibitory effect on transmitter release. These findings suggest that nociceptin, via its pre- and postsynaptic actions, has the potential t o modulate the analgesic, behavioral, and autonomic functions of the P AG.