The present experiments investigated the role of neurokinin‐1 (NK1) and neurokinin‐3 (NK3) receptors on the activity of the locus coeruleus (LC)‐noradrenergic system by using a dual probe microdialysis technique in anesthetized guinea pigs. The local application in the LC of the selective NK1 receptor agonists [SAR9,Met(O2)11]‐SP (10 μM) and septide (1 μM) as well as the selective NK3 receptor agonist senktide (1 μM), enhanced the extracellular norepinephrine (NE) levels in the prefrontal cortex. The enhancing effect of [SAR9,Met(O2)11]‐SP was completely blocked by the peripheral administration of the selective non peptide NK1 and NK3 receptor antagonists, GR 205171 (1 mg/kg, i.p.) and SR 142801 (0.1 mg/kg, i.p.), respectively, whereas SR 142806 (0.1 mg/kg, i.p.) the inactive enantiomer of SR 142801 had no effect. Moreover, the [SAR9,Met(O2)11]‐SP‐induced increase in LC DOPAC concentrations, is only antagonized by GR 205171. In contrast, only SR 142801 (0.3 mg/kg, i.p.) could block stereoselectively the senktide‐evoked increase in NE levels. Both [SAR9,Met(O2)11]‐SP and senktide effects were blocked by local infusion into the LC of SR 142801 (10−9 M). These results demonstrate that stimulation of NK1 and NK3 receptors located in the LC area modulates the activity of the LC‐NE system, and that the excitatory effects of NK1 receptor agonists require NKB/NK3 receptor activation in the LC. Synapse 43:62–69, 2002. © 2001 Wiley‐Liss, Inc.
Synapse – Wiley
Published: Jan 1, 2002
Keywords: ; ; ; ;
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