Effects of nociceptinNH2 and [Nphe1]nociceptin(1-13)NH2 on rat brain noradrenaline release in vivo and in vitro.

We have investigated the effects of nociceptin/orphanin FQ (NC) receptor agonist NCNH2 and a competitive NC receptor antagonist, [Nphe1]NC(1-13)NH2 on noradrenaline (NA) release in vivo using microdialysis in freely moving animals and in vitro from cerebrocortical slices. One nmol of NCNH2 injected into rat locus coeruleus inhibited NA release from the prefrontal cortex (E(max) 27.4+/-5.7% 30 min after injection) which was partially (33%) reversed by 100 nmol of [Nphe1]NC(1-13)NH2. In cerebrocortical slices NCNH2 inhibited NA release in a concentration-dependent manner (EC50 12 nM, E(max) 29.4%) that was reversed by [Nphe1]NC(1-13)NH2. In both preparations, [Nphe1]NC(1-13)NH2 per se was inactive. These data demonstrate an inhibition of NA release by NCNH2 in a [Nphe1]NC(1-13)NH2 sensitive manner in both in vivo brain microdialysis and in vitro cerebrocortical slices studies in rats.