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

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. GABA_A 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.