Nociceptin/orphanin FQ and [Pheψ(CH2-NH)Gly]nociceptin(1–13)NH2 modulates the activity of hypothalamic paraventricular nucleus neurons in vitro

Nociceptin, also known as orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like₁ (ORL₁) receptor, is moderately expressed in the hypothalamic paraventricular nucleus (PVN) involved in the integrative control of the function of the endocrine and autonomic nervous systems. Our previous study demonstrated that intracerebroventricular administration of N/OFQ elicits an inhibitory action on the function of the cardiovascular and sympathetic nervous systems in conscious rats. However, the effects of N/OFQ on PVN neurons have not been examined. We investigated the effects of N/OFQ on PVN neurons using a whole-cell patch-clamp recording technique in rat brain slices. N/OFQ (30–1000 nM) hyperpolarized membrane potentials in type 1 and type 2 neurons of the PVN classified by the electrophysiological property. [Phe¹ψ(CH₂-NH)Gly²]nociceptin(1-13)NH₂ (Pheψ) (1–9 μM), a presumed competitive antagonist of the ORL₁ receptor, also hyperpolarized membrane potential in both types of neurons. In voltage clamp studies, N/OFQ (3–3000 nM) activated a K⁺ current concentration-dependently in 69.7% of PVN neurons with an EC₅₀ of 72.4±12 nM. Pheψ (100–9000 nM) also activated a K⁺ current with an EC₅₀ of 818±162 nM in PVN neurons, and significantly reduced the amplitude of the N/OFQ-stimulated current. The N/OFQ-induced current was not antagonized by the classical opioid receptor antagonist naloxone and putative antagonist nocistatin. These findings suggest that N/OFQ may have a functional role in the PVN.