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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2001-10-5
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pubmed:abstractText |
Antagonists at substance P receptors of the neurokinin 1 (NK1) type have been shown to represent a novel class of antidepressant drugs, with comparable clinical efficacy to the selective serotonin (5-HT) reuptake inhibitors (SSRIs). Because 5-HT(1A) receptors may be critically involved in the mechanisms of action of SSRIs, we examined whether these receptors could also be affected in a model of whole-life blockade of NK1 receptors, i.e. knock-out mice lacking the latter receptors (NK1-/-). 5-HT(1A) receptor labeling by the selective antagonist radioligand [(3)H]N-[2-[4-(2-methoxyphenyl)1-piperazinyl]-ethyl]-N-(2-pyridinyl)-cyclohexanecarboxamide (WAY 100635) and 5-HT(1A)-dependent [(35)S]GTP-gamma-S binding at the level of the dorsal raphe nucleus (DRN) in brain sections, as well as the concentration of 5-HT(1A) mRNA in the anterior raphe area were significantly reduced (-19 to -46%) in NK1-/- compared with NK1+/+ mice. Furthermore, a approximately 10-fold decrease in the potency of the 5-HT(1A) receptor agonist ipsapirone to inhibit the discharge of serotoninergic neurons in the dorsal raphe nucleus within brainstem slices, and reduced hypothermic response to 8-OH-DPAT, were noted in NK1-/- versus NK1+/+ mice. On the other hand, cortical 5-HT overflow caused by systemic injection of the SSRI paroxetine was four- to sixfold higher in freely moving NK1-/- mutants than in wild-type NK1+/+ mice. Accordingly, the constitutive lack of NK1 receptors appears to be associated with a downregulation/functional desensitization of 5-HT(1A) autoreceptors resembling that induced by chronic treatment with SSRI antidepressants. Double immunocytochemical labeling experiments suggest that such a heteroregulation of 5-HT(1A) autoreceptors in NK1-/- mutants does not reflect the existence of direct NK1-5-HT(1A) receptor interactions in normal mice.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-Hydroxy-2-(di-n-propylamino)tetral...,
http://linkedlifedata.com/resource/pubmed/chemical/Antidepressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Autoreceptors,
http://linkedlifedata.com/resource/pubmed/chemical/Paroxetine,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurokinin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT1,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Substance P,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100635,
http://linkedlifedata.com/resource/pubmed/chemical/ipsapirone
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1529-2401
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pubmed:author |
pubmed-author:AlbertiII,
pubmed-author:BondHH,
pubmed-author:De FelipeCC,
pubmed-author:FrogetLL,
pubmed-author:GardierA MAM,
pubmed-author:HánaII,
pubmed-author:HamonMM,
pubmed-author:HuntS PSP,
pubmed-author:JacquotCC,
pubmed-author:LanfumeyLL,
pubmed-author:MoratallaRR,
pubmed-author:RupniakN MNM
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8188-97
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11588191-8-Hydroxy-2-(di-n-propylamino)tetralin,
pubmed-meshheading:11588191-Animals,
pubmed-meshheading:11588191-Antidepressive Agents,
pubmed-meshheading:11588191-Autoreceptors,
pubmed-meshheading:11588191-Drug Resistance,
pubmed-meshheading:11588191-Electrophysiology,
pubmed-meshheading:11588191-Immunohistochemistry,
pubmed-meshheading:11588191-Male,
pubmed-meshheading:11588191-Mice,
pubmed-meshheading:11588191-Mice, Knockout,
pubmed-meshheading:11588191-Neurons,
pubmed-meshheading:11588191-Paroxetine,
pubmed-meshheading:11588191-Piperazines,
pubmed-meshheading:11588191-Pyridines,
pubmed-meshheading:11588191-Pyrimidines,
pubmed-meshheading:11588191-RNA, Messenger,
pubmed-meshheading:11588191-Raphe Nuclei,
pubmed-meshheading:11588191-Receptors, Neurokinin-1,
pubmed-meshheading:11588191-Receptors, Serotonin,
pubmed-meshheading:11588191-Receptors, Serotonin, 5-HT1,
pubmed-meshheading:11588191-Serotonin Antagonists,
pubmed-meshheading:11588191-Serotonin Receptor Agonists,
pubmed-meshheading:11588191-Serotonin Uptake Inhibitors,
pubmed-meshheading:11588191-Substance P
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pubmed:year |
2001
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pubmed:articleTitle |
5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P (neurokinin 1) receptor knock-out mice mimic antidepressant-induced desensitization.
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pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale U288, Neuropsychopharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, 75013 Paris, France. nifroger@ext.jussieu.fr
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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