Modification of acetylcholine release by nociceptin in conscious rat striatum.

Nociceptin (NOC), an endogenous ligand for the orphan opioid receptor ORL1 (ORL1), has recently been recognized as a neuropeptide. We used brain microdialysis and on-line high performance liquid chromatography (HPLC) to examine the effect of NOC on the basal outflow of acetylcholine (ACh) in the freely moving rat striatum in vivo. ACh release was reduced by nociceptin at a concentration of 10(-5) M to 79% of control release. This effect of NOC was attenuated by [Phe1Psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2 (PhePsi), suggesting that NOC activates the ORL1 receptor and (PhePsi) acts as an antagonist on ORL1 in rat striatum in vivo. These findings indicate that NOC may act as a neuropeptide which inhibits ACh release in the striatum via ORL1.