Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more

Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats

“…At the intracellular level, however, the activation of membrane NOP receptors exerts actions similar to those induced by activation of the other opioid receptors, namely, inhibition of cAMP production, closure of voltage-sensitive Ca ++ channels and enhancement of an outward K + conductance (Meunier et al 1995;Reinscheid et al 1995Reinscheid et al , 1998. Nevertheless, naloxone, a non-selective opioid antagonist, does not block N/OFQ intracellular events (Henderson and McKnight 1997;Darland et al 1998), confirming that the pharmacological actions of this peptide are not mediated by the classic opioid receptors.…”

[Nphe1]‐Nociceptin (1‐13)‐NH2, a nociceptin receptor antagonist, reverses nociceptin‐induced spatial memory impairments in the Morris water maze task in rats

“…Moreover, in situ hybridization and immunohistochemical studies, in rodents, have demonstrated that both OP 4 / nociceptin mRNA and receptor protein are found in high concentrations in the hippocampus, brainstem and cortex, areas of the brain involved in higher functions including learning and memory processing (Henderson & McKnight, 1997;Meunier, 1997;Darland et al, 1998).…”

(8‐Naphthalen‐1‐ylmethyl‐4‐oxo‐1‐phenyl‐1,3,8‐triaza‐spiro[4.5]dec‐3‐yl)‐acetic acid methyl ester (NNC 63‐0532) is a novel potent nociceptin receptor agonist

“…Nociceptin, also known as orphanin FQ, has been identi®ed as a naturally occurring agonist of ORL1 and is a heptadecapeptide structurally similar to dynorphin A, but lacking the Nterminal tyrosine essential for activation of traditional (m,k,d) opioid receptors . Nociceptin has been frequently used to study the physiological roles of ORL1 and it is now clear that this receptor is implicated in a variety of functions in the periphery (e.g., vascular contraction, control of heart rate, water retention, pain perception) and in brain (e.g., memory and learning, pain sensation, control of appetite) (Darland et al, 1998;. However, in brain and periphery these studies are complicated by the labile nature of nociceptin in vivo and in studies of its central e ects by the inability of nociceptin to cross the blood brain barrier.…”