Inhibition of rat oxytocin and vasopressin supraoptic nucleus neurons by nociceptin in vitro

Abstract

The effects of nociceptin (orphanin FQ) on the excitability of electrophysiologically-identified oxytocin and vasopressin neurons were investigated in rat hypothalamic supraoptic nucleus slices in vitro, using whole-cell patch-clamp recording techniques. Nociceptin inhibited the spontaneous discharge of 9/20 (45%) of supraoptic nucleus neurons tested, while in the remaining 11/20 neurons it inhibited firing rate and induced repetitive burst-firing. There were no differences between the effects of nociceptin on oxytocin and vasopressin neurons. When recordings were made using EGTA-containing patch pipettes, nociceptin caused inhibition in all 30 supraoptic nucleus neurons tested, and burst-firing was not seen. The inhibitory effects of nociceptin persisted in low Ca, Co medium, and were not antagonized by naloxone at concentrations sufficient to antagonize the inhibitory actions of morphine and U50 488. The actions of nociceptin on supraoptic nucleus neurons are therefore likely to be mediated by postsynaptic opioid receptor-like (ORL 1) receptors that are distinct from known opioid receptors. The inhibitory responses to nociceptin were also insensitive to naloxone benzoylhydrazone, which itself had no effect on the spontaneous discharge of the supraoptic nucleus neurons. Our findings demonstrate that endogenous nociceptin may have a functional role in regulating oxytocin and vasopressin secretion through its actions on hypothalamic supraoptic nucleus neurons.