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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
The serotonin transporter (5-HTT) plays a key role in the regulation of serotonin (5-hydroxytryptamine, 5-HT) transmission in the pathophysiology and therapeutics of several psychiatric disorders. The mean spontaneous firing rate of midbrain dorsal raphe 5-HT neurons was recorded in chloral hydrate-anesthetized mice. The serotonin transporter (5-HTT), which plays a key role in the regulation of serotonin was significantly decreased in homozygous mice lacking the 5-HT transporter (5-HTT -/-) by 66% and in heterozygous (5-HTT +/-) mice by 36% compared with their normal littermates (5-HTT +/+). Systemic injection of the selective 5-HT(1A) receptor antagonist WAY 100635 enhanced 5-HT neuronal firing by 127% in 5-HT -/- mice, thus indicating an enhanced synaptic availability of 5-HT at inhibitory 5-HT(1A) receptors. Nevertheless, the cell body 5-HT(1A) autoreceptors were desensitized in both 5-HTT -/- and 5-HTT +/- mice. At the postsynaptic level, the recovery time (RT(50)) of the firing rate of hippocampus CA(3) pyramidal neurons following iontophoretic applications of 5-HT was significantly prolonged only in 5-HTT -/- mice. The selective 5-HT reuptake inhibitor paroxetine significantly prolonged the RT(50) in 5-HTT +/+ and 5-HTT +/- mice, without altering the maximal inhibitory effect of 5-HT. These neurons in 5-HTT -/- mice showed an attenuated response to the 5-HT(1A) agonist 8-hydroxy-2-diproplyaminotetralin, but not to 5-HT itself. These results establish that the lack of 5-HTT causes a prolonged recovery of firing activity following 5-HT applications. The genetic deletion of the 5-HTT plays a key role on 5-HT(1A) receptor adaptation: a desensitization at pre- and postsynaptic levels in 5-HTT -/- mice, but to a different extent, and only at the presynaptic level in the 5-HTT +/- group.
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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/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
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/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100635
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-3565
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
987-95
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11181933-8-Hydroxy-2-(di-n-propylamino)tetralin,
pubmed-meshheading:11181933-Animals,
pubmed-meshheading:11181933-Carrier Proteins,
pubmed-meshheading:11181933-Electrophysiology,
pubmed-meshheading:11181933-Hippocampus,
pubmed-meshheading:11181933-Infusions, Intravenous,
pubmed-meshheading:11181933-Membrane Glycoproteins,
pubmed-meshheading:11181933-Membrane Transport Proteins,
pubmed-meshheading:11181933-Mice,
pubmed-meshheading:11181933-Mice, Knockout,
pubmed-meshheading:11181933-Nerve Tissue Proteins,
pubmed-meshheading:11181933-Neurons,
pubmed-meshheading:11181933-Paroxetine,
pubmed-meshheading:11181933-Piperazines,
pubmed-meshheading:11181933-Pyramidal Tracts,
pubmed-meshheading:11181933-Pyridines,
pubmed-meshheading:11181933-Raphe Nuclei,
pubmed-meshheading:11181933-Receptors, Serotonin,
pubmed-meshheading:11181933-Serotonin,
pubmed-meshheading:11181933-Serotonin Antagonists,
pubmed-meshheading:11181933-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:11181933-Serotonin Receptor Agonists,
pubmed-meshheading:11181933-Serotonin Uptake Inhibitors,
pubmed-meshheading:11181933-Time Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Modifications of the serotonergic system in mice lacking serotonin transporters: an in vivo electrophysiological study.
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pubmed:affiliation |
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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