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Titolo:
IN-VIVO EFFECTS OF THE SIMULTANEOUS BLOCKADE OF SEROTONIN AND NOREPINEPHRINE TRANSPORTERS ON SEROTONERGIC FUNCTION - MICRODIALYSIS STUDIES
Autore:
BEL N; ARTIGAS F;
Indirizzi:
CSIC,INST INVEST BIOMED,DEPT NEUROCHEM,JORDI GIRONA 18-26 BARCELONA 08034 SPAIN CSIC,INST INVEST BIOMED,DEPT NEUROCHEM BARCELONA 08034 SPAIN
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 278, anno: 1996,
pagine: 1064 - 1072
SICI:
0022-3565(1996)278:3<1064:IEOTSB>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DORSAL RAPHE NEURONS; INCREASES EXTRACELLULAR SEROTONIN; ANTIDEPRESSANT BINDING-SITES; FREELY-MOVING RATS; HUMAN-BRAIN; MAJOR DEPRESSION; FRONTAL-CORTEX; 5-HYDROXYTRYPTAMINE RELEASE; RECEPTOR REGULATION; UPTAKE INHIBITORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
73
Recensione:
Indirizzi per estratti:
Citazione:
N. Bel e F. Artigas, "IN-VIVO EFFECTS OF THE SIMULTANEOUS BLOCKADE OF SEROTONIN AND NOREPINEPHRINE TRANSPORTERS ON SEROTONERGIC FUNCTION - MICRODIALYSIS STUDIES", The Journal of pharmacology and experimental therapeutics, 278(3), 1996, pp. 1064-1072

Abstract

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 (ED(50), 11 mu M), 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 mu M 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 (181 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 reuptakeinhibitors 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 elevationinduced 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 notin 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 repealed treatment. The elevations noted in the frontal cortex after the higher doses of imipramine may reflect the involvement of the noradrenergic system.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:41:42