Postsynaptic Mechanisms Underlying Responsiveness of Amygdaloid Neurons to Nociceptin/Orphanin FQ

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Abstract
Effects of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor (ORL), were investigated in the rat lateral (AL) and central (ACe) amygdala in vitro. Approximately 98% of presumed projection neurons in the AL responded to N/OFQ with an increase in inwardly rectifying potassium conductance, resulting in an impairment in cell excitability. Half-maximal effects were obtained at 30.6 nm; the Hill coefficient was 0.63. In the ACe, 31% of the cells displayed responses similar to that in the AL, 44% were nonresponsive, and 25% responded with a small potassium current with a linear current–voltage relationship. Responses to N/OFQ were reduced by 100 μmBa2+, were insensitive to 10 μmnaloxone, and were blocked by a selective ORL antagonist, [Phe1ψ(CH2-NH)Gly2]NC(1–13)NH2(IC50 = 760 nm). Involvement of G-proteins was indicated by irreversible effects and blockade of action of N/OFQ during intracellular presence of GTP-γ-S (100 μm) and GDP-β-S (2 mm), respectively, and prevention of responses after incubation in pertussis toxin (500 ng/ml). These mechanisms may contribute to the role of N/OFQ in the reduction of fear responsiveness and stress that have recently been suggested on the basis of histochemical and behavioral studies.