Control of glutamate and GABA release by nociceptin/orphanin FQ in the rat lateral amygdala

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Abstract
1 The actions of the heptadecapeptide termed nociceptin or orphanin FQ (N/OFQ) and the recently discovered putative precursor product nocistatin were examined on synaptic transmission in putative projection cells of the rat lateral amygdala using the whole-cell patch-clamp technique. 2 N/OFQ decreased evoked non-NMDA receptor-mediated excitatory postsynaptic current (EPSC) amplitudes in a concentration-dependent manner, with a half-maximal inhibitory effect elicited by 21.8 ± 7.5 nm and a Hill coefficient of 0.8 ± 0.2 (n= 22. Responses were maximally suppressed to 70.3 ± 1.7 % of the control value. The effect of N/OFQ was prevented by 1 μm[Phe1ψ(CH2-NH)Gly2]NC(1-13)NH2 (PheψN/OFQ), a substance known as an antagonist/partial agonist of the ORL receptor. 3 GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) elicited through intra-amygdaloid stimulation were reduced to 48.0 ± 6.8 % by 1 μm N/OFQ (n= 5. 4 Nocistatin had no measurable effect on evoked synaptic currents or membrane properties of recorded neurons. 5 N/OFQ reduced the frequency of spontaneous miniature EPSCs and IPSCs to 74.0 ± 2.6 % and 84.4 ± 1.1 %, respectively, without affecting the amplitudes. 6 The present findings indicate that N/OFQ, but not nocistatin, inhibits the release of glutamate and GABA in the lateral amygdala, presumably by acting on presynaptic release sites. These mechanisms may add to the role of N/OFQ in reducing stress vulnerability as recently proposed on the basis of behavioural and genetic approaches.