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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1996-11-5
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| pubmed:abstractText |
The effects of the blockade of serotonin (5-HT) and norepinephrine (NE) transporters on extracellular 5-HT (5-HText) have been examined using in vivo microdialysis in conscious rats. Locally infused, imipramine increased 5-HText dose-dependently in raphe nuclei and frontal cortex. The potency was identical (ED50 11 microM), although greater elevations were noted in the raphe nuclei (e.g., 74.5 +/- 16.9 vs. 41.1 +/- 4.5 fmol/fraction in the frontal cortex at 33 microM imipramine). The i.p. administration of imipramine at 4, 10 and 20 mg/kg increased 5-HText dose-dependently in the frontal cortex to concentrations as high as 390% of basal values. The lowest dose of imipramine significantly increased 5-HText in the raphe, but not in the frontal cortex (187 vs. 120% of basal values, respectively), but higher doses did not cause substantially greater increases in the raphe. The lowest dose affected 5-HText in a manner comparable to 1 mg/kg of the selective 5-HT reuptake inhibitors citalopram and fluvoxamine. The noradrenergic system may participate in the cortical elevations seen after 10 and 20 mg/kg of imipramine, because 10 mg/kg of desipramine significantly increased 5-HText in the frontal cortex, but not the raphe nuclei, of fluoxetine-treated rats (from 8.6 +/- 1.4 to 13.3 +/- 1.9 fmol/fraction; prefluoxetine values: 4.3 +/- 0.6 fmol/fraction, n = 11). Desipramine alone (10 mg/kg i.p.) did not modify 5-HText in the frontal cortex. The elevation induced by desipramine in fluoxetine-treated rats does not seem to involve changes in the activation of alpha-2 adrenoceptors, as it was still present in rats pretreated with 0.2 mg/kg i.p. of RX-821002, a selective antagonist of alpha-2 adrenoceptors. Moreover, clonidine, an alpha-2 adrenoceptor agonist, significantly reduced 5-HText in fluoxetine-treated rats when infused locally in the cortex, but it did not modify the effects of the systemic administration of desipramine, providing a further indication that alpha-2 heteroreceptors in 5-HT terminals do not participate in the effects of desipramine. When given for 2 weeks, 4 mg/kg day of imipramine significantly elevated 5-HText in the frontal cortex (from 7.7 +/- 1.2 to 20.0 +/- 5.8 fmol/fraction), but not in the raphe nuclei. These results are consistent with previous data suggesting that low doses of antidepressants with serotonergic action enhance 5-HText in the frontal cortex only after repeated treatment. The elevations noted in the frontal cortex after the higher doses of imipramine may reflect the involvement of the noradrenergic system.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Citalopram,
http://linkedlifedata.com/resource/pubmed/chemical/Clonidine,
http://linkedlifedata.com/resource/pubmed/chemical/Desipramine,
http://linkedlifedata.com/resource/pubmed/chemical/Fluoxetine,
http://linkedlifedata.com/resource/pubmed/chemical/Fluvoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/Imipramine,
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/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Plasma Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Slc6a4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| 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
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1064-72
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:8819487-Adrenergic Uptake Inhibitors,
pubmed-meshheading:8819487-Animals,
pubmed-meshheading:8819487-Carrier Proteins,
pubmed-meshheading:8819487-Cerebral Cortex,
pubmed-meshheading:8819487-Citalopram,
pubmed-meshheading:8819487-Clonidine,
pubmed-meshheading:8819487-Desipramine,
pubmed-meshheading:8819487-Fluoxetine,
pubmed-meshheading:8819487-Fluvoxamine,
pubmed-meshheading:8819487-Imipramine,
pubmed-meshheading:8819487-Male,
pubmed-meshheading:8819487-Membrane Glycoproteins,
pubmed-meshheading:8819487-Membrane Transport Proteins,
pubmed-meshheading:8819487-Microdialysis,
pubmed-meshheading:8819487-Nerve Tissue Proteins,
pubmed-meshheading:8819487-Norepinephrine,
pubmed-meshheading:8819487-Norepinephrine Plasma Membrane Transport Proteins,
pubmed-meshheading:8819487-Raphe Nuclei,
pubmed-meshheading:8819487-Rats,
pubmed-meshheading:8819487-Rats, Wistar,
pubmed-meshheading:8819487-Serotonin,
pubmed-meshheading:8819487-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:8819487-Serotonin Uptake Inhibitors,
pubmed-meshheading:8819487-Symporters
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| pubmed:year |
1996
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| pubmed:articleTitle |
In vivo effects of the simultaneous blockade of serotonin and norepinephrine transporters on serotonergic function. Microdialysis studies.
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| pubmed:affiliation |
Department of Neurochemistry, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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