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Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response.
- Source :
-
Journal of psychiatry & neuroscience : JPN [J Psychiatry Neurosci] 2004 May; Vol. 29 (3), pp. 208-18. - Publication Year :
- 2004
-
Abstract
- Substance P (neurokinin-1 [NK1]) receptor antagonists appear to be effective antidepressant and anxiolytic agents, as indicated in 3 double-blind clinical trials. In laboratory animals, they promptly attenuate the responsiveness of serotonin (5-hydroxytryptamine [5-HT]) and norepinephrine (NE) neurons to agonists of their cell-body autoreceptors, as is the case for some antidepressant drugs that are currently in clinical use. Long-term, but not subacute, antagonism of NK1 receptors in rats increases 5-HT transmission in the hippocampus, a property common to all antidepressant treatments tested thus far. This enhancement seems to be mediated by a time-dependent increase in the firing rate of 5-HT neurons. Mice with the NK1 receptor deleted from their genetic code also have an increased firing rate of 5-HT neurons. Taken together, these observations strongly suggest that NK1 antagonists could become a new class of antidepressant and anxiolytic agents.
- Subjects :
- Adrenergic alpha-Agonists pharmacology
Animals
Antiemetics pharmacology
Aprepitant
Autoreceptors drug effects
Autoreceptors metabolism
Electrophysiology instrumentation
Hippocampus drug effects
Hippocampus metabolism
Locus Coeruleus metabolism
Mice
Mice, Mutant Strains
Morpholines pharmacology
Neurokinin-1 Receptor Antagonists
Phenylephrine pharmacology
Photomicrography
Raphe Nuclei metabolism
Receptors, Neurokinin-1 metabolism
Anxiety drug therapy
Depressive Disorder, Major drug therapy
Norepinephrine antagonists & inhibitors
Receptors, Neurokinin-1 drug effects
Serotonin metabolism
Substance P antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1180-4882
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of psychiatry & neuroscience : JPN
- Publication Type :
- Academic Journal
- Accession number :
- 15173897