PMID- 15030410 OWN - NLM STAT- MEDLINE DCOM- 20040426 LR - 20231213 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 89 IP - 1 DP - 2004 Apr TI - Exogenous, but not endogenous nociceptin modulates mesolimbic dopamine release in mice. PG - 257-63 AB - The effect of nociceptin (an endogenous ligand of the ORL1 receptor) on mesolimbic dopamine release and simultaneous horizontal locomotion was studied in freely moving mice undergoing microdialysis of the nucleus accumbens. Intracerebroventricular (i.c.v.) administration of nociceptin (7 nmol) induced a long-lasting suppression of mesolimbic dopamine release and horizontal locomotion in wild-type but not ORL1 knockout mice. I.c.v. administration of the recently reported peptide nociceptin antagonist [Nphe1, Arg14, Lys15] nociceptin-NH(2) (known also as UFP-101, 5 nmol) completely abolished the suppressive effect of nociceptin on mesolimbic dopamine release. However, UFP-101 administration alone induced a mild and lasting suppression of mesolimbic dopamine release in both wild-type and ORL1 knockout mice that was magnified in ORL1 knockout mice by coadministration of nociceptin. UFP-101 administration alone suppressed locomotion in both genotypes. These results confirm that the suppressive action of nociceptin on mesolimbic dopamine release is mediated entirely by the ORL1 receptor, and that UFP-101 effectively antagonizes this action. However, the lack of a stimulatory effect of UFP-101 in wild-type mice indicates that despite being sensitive to exogenous nociceptin action, basal mesolimbic dopaminergic activity is not determined by endogenous nociceptin in mice. FAU - Koizumi, Miwako AU - Koizumi M AD - Neural Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Saitama, Japan. FAU - Midorikawa, Naoko AU - Midorikawa N FAU - Takeshima, Hiroshi AU - Takeshima H FAU - Murphy, Niall P AU - Murphy NP LA - eng PT - Journal Article PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 ((Nphe(1),Arg(14),Lys(15))N-OFQ NH(2)) RN - 0 (Ligands) RN - 0 (Opioid Peptides) RN - 0 (Receptors, Opioid) RN - VTD58H1Z2X (Dopamine) RN - 0 (Nociceptin Receptor) RN - 0 (Oprl1 protein, mouse) SB - IM MH - Animals MH - Dopamine/*metabolism MH - Female MH - Injections, Intraventricular MH - Ligands MH - Male MH - Mice MH - Mice, Knockout MH - Microdialysis MH - Motor Activity/drug effects MH - Nucleus Accumbens/*drug effects/*metabolism MH - Opioid Peptides/administration & dosage/antagonists & inhibitors/*metabolism/*pharmacology MH - Receptors, Opioid/genetics MH - Nociceptin Receptor MH - Nociceptin EDAT- 2004/03/20 05:00 MHDA- 2004/04/27 05:00 CRDT- 2004/03/20 05:00 PHST- 2004/03/20 05:00 [pubmed] PHST- 2004/04/27 05:00 [medline] PHST- 2004/03/20 05:00 [entrez] AID - JNC2322 [pii] AID - 10.1111/j.1471-4159.2003.02322.x [doi] PST - ppublish SO - J Neurochem. 2004 Apr;89(1):257-63. doi: 10.1111/j.1471-4159.2003.02322.x.