Stereoselective and region-specific induction of immediate early gene
expression in rat parietal cortex by blockade of neurokinin 1 receptors
Florence Serres1,
Simone B. Sartori2,
Anna Halton1,
Qi Pei1,
Catherine Rochat3,
Nicolas Singewald2,
Trevor Sharp1,
Mark J. Millan3*
1 University Department of Pharmacology, Oxford, UK
2 Department of Pharmacology and Toxicology, Institute of Pharmacy,
University of Innsbruck, Innsbruck, Austria
3 I.d.R. Servier, 125 chemin de Ronde, 78290 Croissy/Seine, France
* To whom correspondence should be addressed.
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Abstract |
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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.
Key Words:
NK1 receptor, rat, c-fos, Arc, in situ hybridization, immunocytochemistry
