title: Kainate seizures increase nociceptin/orphanin FQ release in the rat hippocampus and thalamus: a microdialysis study.
abstract: The neuropeptide nociceptin/orphanin FQ (N/OFQ) has been suggested to play a facilitatory role in kainate seizure expression. Furthermore, mRNA levels for the N/OFQ precursor are increased following kainate seizures, while its receptor (NOP) density is decreased. These data suggest increased N/OFQ release. To obtain direct evidence that this is the case, we have developed a microdialysis technique, coupled with a sensitive radioimmunoassay, that allows measurement of N/OFQ release from the hippocampus and thalamus of awake, freely moving animals. In both these brain areas, the spontaneous N/OFQ efflux decreased by approximately 50% and 65% when Ca2+ was omitted and when tetrodotoxin was added to the perfusion medium, respectively. Perfusion of the dialysis probe with high K+ increased N/OFQ release (approximately threefold) in a Ca2+-dependent and tetrodotoxin-sensitive manner. Kainate seizures caused a twofold increase in N/OFQ release followed, within 3 h, by a return to baseline levels. Approximately 5 h after kainate, a late increase in N/OFQ release was observed. On the following day, when animals were having only low grade seizures, N/OFQ release was not significantly different from normal. These phenomena were observed with similar patterns in the hippocampus and in the thalamus. The present data indicate that acute limbic seizures are associated with increased N/OFQ release, which may prime the molecular changes described above, i.e. cause down-regulation of NOP receptors and activation of N/OFQ biosynthesis.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Ferrara, Italy.
authors.forename: Liliana Carmona
authors.initials: LC
authors.lastname: Aparicio
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.forename: Anna
authors.initials: A
authors.lastname: Binaschi
authors.forename: Manuela
authors.initials: M
authors.lastname: Mazzuferi
authors.forename: Simona
authors.initials: S
authors.lastname: Mantovani
authors.forename: Manuela
authors.initials: M
authors.lastname: Di Benedetto
authors.forename: Daniela
authors.initials: D
authors.lastname: Landuzzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lopetuso
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
authors.forename: Michele
authors.initials: M
authors.lastname: Simonato
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D004569:Electroencephalography / Q000379:methods; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D017551:Microdialysis / Q000379:methods*; D018847:Opioid Peptides / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D000097629:Nociceptin
chemical_list: D007608:Kainic Acid; D018847:Opioid Peptides; D011188:Potassium; D000097629:Nociceptin