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Titolo:
Enhancement of 5-HT1B and 5-HT1D receptor antagonist effects on extracellular 5-HT levels in the guinea-pig brain following concurrent 5-HT1A or 5-HTre-uptake site blockade
Autore:
Roberts, C; Boyd, DF; Middlemiss, DN; Routledge, C;
Indirizzi:
SmithKline Beecham Pharmaceut, Dept Neurosci, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AW ssex, England
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 9, volume: 38, anno: 1999,
pagine: 1409 - 1419
SICI:
0028-3908(199909)38:9<1409:EO5A5R>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; IN-VIVO MICRODIALYSIS; DORSAL RAPHE NUCLEUS; CEREBRAL BLOOD-FLOW; FRONTAL-CORTEX; GLUCOSE-METABOLISM; REUPTAKE INHIBITOR; DEPRESSED-PATIENTS; MAJOR DEPRESSION; RAT DORSAL;
Keywords:
microdialysis; guinea-pig; 5-HT1B/1D; 5-HT1A; receptor antagonists;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Roberts, C SmithKline Beecham Pharmaceut, Dept Neurosci, New Frontiers SciPk,3rd Ave, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut New Frontiers Sci Pk,3rd Ave Harlow Essex England CM19 5AW
Citazione:
C. Roberts et al., "Enhancement of 5-HT1B and 5-HT1D receptor antagonist effects on extracellular 5-HT levels in the guinea-pig brain following concurrent 5-HT1A or 5-HTre-uptake site blockade", NEUROPHARM, 38(9), 1999, pp. 1409-1419

Abstract

The effects of selective serotonin re-uptake inhibitor (SSRI), paroxetine,and 5-HT1A, 5-HT1B and 5-HT1B/1D receptor antagonists on in vivo extracellular 5-HT levels in the guinea-pig frontal cortex and dorsal hippocampus were investigated using the technique of microdialysis, The aim of the study was to further investigate the autoreceptor roles of the 5-HT1A, 5-HT1B and5-HT1D receptors in the median vs dorsal raphe nuclei. In the frontal cortex, 5-HT1A (WAY 100635, 1 mg/kg i.p.) or 5-HT1B (SB-224289, 4 mg/kg i.p.) receptor antagonists had no effect on extracellular levels of 5-HT, whilst the mixed 5-HT1B/1D receptor antagonist (GR 127935, 0.3 mg/kg i.p) produced a significant decrease in extracellular 5-HT levels. Paroxetine (10 mu M) significantly increased extracellular 5-HT levels when perfused locally intothe cortex. Administration of 3B-224289, followed 120 min later by WAY 100635, had no effect on extracellular 5-HT levels. In contrast, sequential administration of either WAY 100635 and GR 127935, or SB-224289 and paroxetine significantly increased extracellular 5-HT levels. In the dorsal hippocampus, whilst 5-HT1A receptor antagonism elicited by administration of WAY 100635 had no effect, both 5-HT1B and mixed 5-HT1B/1D receptor blockade significantly increased extracellular 5-HT levels. Administration of SE-224289 followed 120 min later with WAY 100635, or WAY 100635 followed 30 min later with GR 127935, potentiated the effect of the three compounds alone, significantly increasing extracellular 5-HT levels. These data demonstrate that to simultaneously increase extracellular 5-HT in both frontal cortex and dorsal hippocampus of the guinea-pig brain concurrent 5-HT1A, 5-HT1B and 5-HT1D receptor blockade is required. Whereas in the dorsal hippocampus, 5-HT1B receptor blockade is sufficient to elicit an increase in extracellular 5-HTlevels. (C) 1999 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 22:09:24