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

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 postsynapti c current (EPSC) amplitudes in a concentration-dependent manner, with a hal f-maximal inhibitory effect elicited by 21.8 +/- 7.5 nM and a Hill coeffici ent 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 muM [Ph e(1)psi (CH2-NH)Gly(2)]NC(1-3)NH2 (Phe psiN/OFQ), a substance known as an a ntagonist/partial agonist of the ORL receptor. 3. GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) elici ted through intra amygdaloid stimulation were reduced to 48.0 +/- 6.8% by 1 muM N/OFQ (n = 5). 4. Nocistatin had no measurable effect on evoked synaptic currents or membr ane properties of recorded neurons. 5. N/BFQ reduced the frequency of spontaneous miniature EPSCs and IPSCs to 74.0 +/- 2.6% and 84.4 +/- 1.1%, respectively, without affecting the amplit udes. 6. The present findings indicate that N/OFQ, but not nocistatin, inhibits t he release of glutamate and GABA in the lateral amygdala, presumably by act ing 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.