title: Nociceptin/orphanin FQ and opioid receptor-like receptor mRNA expression in dopamine systems.
abstract: Although nociceptin/orphanin FQ (N/OFQ) influences dopamine (DA) neuronal activity, it is not known whether N/OFQ acts directly on DA neurons, indirectly by means of local circuitry, or both. We used two parallel approaches, dual in situ hybridization (ISH) and neurotoxic lesions of DA neurons by using 6-hydroxydopamine (6-OHDA), to ascertain whether N/OFQ and the N/OFQ receptor (NOP) mRNA are expressed in DA neurons in the ventral tegmental area (VTA) and substantia nigra compacta (SNc). In the VTA and SNc, small populations (approximately 6-10%) of N/OFQ-containing neurons coexpressed mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis. Similarly, very few (1-2%) TH-positive neurons contained N/OFQ mRNA signal. A majority of NOP-positive neurons (approximately 75%) expressed TH mRNA and roughly half of the TH-containing neurons expressed NOP mRNA. Many N/OFQ neurons (approximately 50-60%) expressed glutamic acid decarboxylase 65 and 67 mRNAs, markers for gamma-aminobutyric acid (GABA) neurons. In the 6-OHDA lesion studies, NOP mRNA levels were nearly 80 and 85% lower in the VTA and SNc, respectively, on the lesioned side. These lesions appear to lead to compensatory changes, with N/OFQ mRNA levels approximately 60% and 300% higher in the VTA and SNc, respectively, after 6-OHDA lesions. Finally, N/OFQ-stimulated [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate levels were decreased in the VTA and SNc but not the prefrontal cortex after 6-OHDA lesions. Accordingly, it appears that N/OFQ mRNA was found largely on nondopaminergic (i.e., GABA) neurons, whereas NOP mRNA was located on DA neurons. N/OFQ is in a position to influence DA neuronal activity by means of the NOP located on DA neurons.
authors.affiliation: Mental Health Research Institute, University of Michigan Medical Center, 205 Zina Pitcher Place, Ann Arbor, MI 48109-0720, USA. csnorton@umich.edu
authors.forename: Camille S
authors.initials: CS
authors.lastname: Norton
authors.forename: Charles R
authors.initials: CR
authors.lastname: Neal
authors.forename: Suneel
authors.initials: S
authors.lastname: Kumar
authors.forename: Huda
authors.initials: H
authors.lastname: Akil
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Watson
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000235:genetics; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D018847:Opioid Peptides / Q000235:genetics* / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000235:genetics*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D004298:Dopamine; D005968:Glutamate Decarboxylase; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018847:Opioid Peptides; D016627:Oxidopamine; D012333:RNA, Messenger; D011957:Receptors, Opioid; D014446:Tyrosine 3-Monooxygenase; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat