title: Stereoselective and region-specific induction of immediate early gene expression in rat parietal cortex by blockade of neurokinin 1 receptors.
abstract: Antagonists at neurokinin 1 (NK1) receptors are attracting attention as potential treatments for depressive states in light of their actions in behavioural models predictive of antidepressant properties, their modulation of corticolimbic monoaminergic transmission, and their influence upon neural plasticity. Here, we evaluated the influence of NK1 receptor blockade upon two immediate early genes, Arc and c-fos, implicated in mechanisms of synaptic plasticity. Administration of the selective NK1 receptor antagonist, GR 205,171 (40, but not 1, 5 or 10 mg/kg i.p.), elicited a pronounced elevation in mRNA encoding Arc in both outer and inner layers of the parietal cortex of rat brain. This action was region-specific inasmuch as Arc expression did not change in other cortical territories examined including frontal cortex, nor in CA1, CA3 and the dentate gyrus of the hippocampus. In comparison to GR 205,171, its less active isomer GR 226,206 (1-40 mg/kg) did not significantly modify Arc gene expression in parietal cortex or other cortical areas. GR 205,171 (40 mg/kg) also increased the abundance of c-fos mRNA in outer and inner parietal cortex and caused a corresponding increase in c-fos immunoreactivity in this region. GR 226,206 (40 mg/kg i.p.) had no effect on either c-fos mRNA or protein in parietal cortex. In conclusion, administration of GR 205,171 elicits a stereospecific increase in Arc and c-fos expression in rat parietal cortex but not in other cortical regions. These data suggest that the parietal cortex plays a role in the central actions of NK1 receptor antagonists.
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford, UK.
authors.forename: Florence
authors.initials: F
authors.lastname: Serres
authors.forename: Simone B
authors.initials: SB
authors.lastname: Sartori
authors.forename: Anna
authors.initials: A
authors.lastname: Halton
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.forename: Catherine
authors.initials: C
authors.lastname: Rochat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.forename: Trevor
authors.initials: T
authors.lastname: Sharp
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Millan
authors.forename: Mark
authors.initials: M
authors.lastname: Millan
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D002452:Cell Count; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D016761:Oncogene Proteins v-fos / Q000096:biosynthesis / Q000235:genetics; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D016761:Oncogene Proteins v-fos; D010880:Piperidines; D012333:RNA, Messenger; D013777:Tetrazoles; C103207:vofopitant