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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1996-9-18
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pubmed:abstractText |
We reported previously that pharmacological blockade of somatodendritic 5-hydroxytryptamine (5-HT)1A autoreceptors with spiperone, a nonselective 5-HT1A antagonist, increases the spontaneous firing rate of central serotonergic neurons in awake cats. The present study examined the effects of systemic administration of two reportedly selective 5-HT1A receptor antagonists, (S)-WAY-100135 {N-tert-butyl-3-[4-(2-methoxyphenyl) piperazin-1-yl]-2-phenylpropanamide} and its more potent analog WAY-100635 {N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide}, on the single-unit activity of serotonergic neurons in the dorsal raphe nucleus of freely moving cats. In addition, we assessed the antagonist action of these compounds at the 5-HT1A autoreceptor by examining their ability to block the inhibition of serotonergic neuronal activity produced by systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin, a highly selective 5-HT1A agonist. Administration of (S)-WAY-100135 (0.025-1.0 mg/kg i.v.) moderately depressed neuronal activity at all doses tested. In contrast, administration of WAY-100635 (0.025-0.5 mg/kg i.v.) significantly increased neuronal activity. The stimulatory action of WAY-100635, like that of spiperone, was evident during wakefulness (when serotonergic neurons typically display a relatively high level of activity) but not during sleep (when serotonergic neurons display little or no spontaneous activity). Pretreatment with (S)-WAY-100135 (0.5 mg/kg i.v.) weakly attenuated the inhibitory action of 8-hydroxy-2-(di-n-propylamino)tetralin. In contrast, WAY-100635 at doses as low as 0.1 mg/kg i.v. completely blocked the action of 8-hydroxy-2-(di-n-propylamino)tetralin. The antagonist action of WAY-100635 at 5-HT1A autoreceptors closely paralleled its ability to increase neuronal activity. Overall, WAY-100635 appears to act as a selective 5-HT1A antagonist, whereas (S)-WAY-100135 does not. The results obtained with WAY-100635 confirm our previous findings obtained with spiperone and further support the hypothesis that 5-HT1A autoreceptor-mediated feedback inhibition operates under physiological conditions.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100135,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100635
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
752-62
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8768728-Animals,
pubmed-meshheading:8768728-Cats,
pubmed-meshheading:8768728-Dose-Response Relationship, Drug,
pubmed-meshheading:8768728-Male,
pubmed-meshheading:8768728-Membrane Potentials,
pubmed-meshheading:8768728-Piperazines,
pubmed-meshheading:8768728-Pyridines,
pubmed-meshheading:8768728-Serotonin,
pubmed-meshheading:8768728-Serotonin Antagonists,
pubmed-meshheading:8768728-Sleep
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pubmed:year |
1996
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pubmed:articleTitle |
WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135.
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pubmed:affiliation |
Department of Psychology, Princeton University, New Jersey, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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