Nociceptin orphanin FQ: Effects on thermoregulation in rats

Nociceptin/orphanin FQ is a 17 amino acid peptide which acts as a potent en dogenous agonist of the opioid receptor-like 1 (ORL1) receptor ORL1 recepto r is a G protein-coupled unique member of the cloned opioid receptor family . We have investigated the effects of nociceptin (1, 10 and 100 nM) on the temperature sensitivity of neurons from the preoptic area of the anterior h ypothalamus (PO/AH) in rat brain slices. The body temperature of male Wista r rats was measured after intrahypothalamic application of nociceptin (1 nM ) via cannulas in the PO/AH. Low dose nociceptin (1 nM) significantly incre ased (p < 0.05) temperature sensitivity (TC) of warm-sensitive PO/AH neuron s, while the high concentration (100 nM) decreased TC in both warm-sensitiv e and temperature-insensitive neurons. Similar agonistic activity was obtai ned after addition of [Phe(1)psi (CH2-NH) Gly(2)]-nociceptin-(1-13)-NH2 (1, 10 and 100 nM), recently proposed to be a selective antagonist of the noci ceptin receptor: Neither antagonism nor additive synergism were observed wh en nociceptin and [Phe(1)psi(CH2-NH) Gly(2)]-nociceptin-(1-13)-NH2 were app lied simultaneously in equimolar concentrations. The selective opioid OP3 r eceptor antagonist CTOP, the selective opioid OP2 receptor antagonist nor-b inaltorphimine and selective opioid OP1 receptor antagonist naltrindol had no influence on the effects of nociceptin on temperature sensitivity in PO/ AH neurons. In vivo experiments showed that nociceptin (1 nM; 1 mu l/rat) s ignificantly decreased body temperature (p < 0.05) between 30 and 60 min af ter intrahypothalamic application. These data are in agreement with the hyp othesis that the specific action of endogenous substances on body temperatu re appears to be closely related to a specific change in the temperature se nsitivity of warm-sensitive PO/AH neurons. (C)1999 Prous Science. All right s reserved.