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Titolo:
Differential effect of local infusion of serotonin reuptake inhibitors in the raphe versus forebrain and the role of depolarization-induced release in increased extracellular serotonin
Autore:
Tao, R; Ma, ZY; Auerbach, SB;
Indirizzi:
Rutgers State Univ, Nelson Biol Labs, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 osci, Piscataway, NJ 08854 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 2, volume: 294, anno: 2000,
pagine: 571 - 579
SICI:
0022-3565(200008)294:2<571:DEOLIO>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; IN-VIVO MICRODIALYSIS; BRAIN MICRODIALYSIS; FRONTAL-CORTEX; 5-HYDROXYINDOLEACETIC ACID; ELECTRICAL-STIMULATION; ANTIDEPRESSANT DRUGS; RAT; INVIVO; 5-HT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Auerbach, SB Rutgers State Univ, Nelson Biol Labs, Dept Cell Biol & Neurosci, 604 Allison Rd, Piscataway, NJ 08854 USA Rutgers State Univ 604 AllisonRd Piscataway NJ USA 08854 USA
Citazione:
R. Tao et al., "Differential effect of local infusion of serotonin reuptake inhibitors in the raphe versus forebrain and the role of depolarization-induced release in increased extracellular serotonin", J PHARM EXP, 294(2), 2000, pp. 571-579

Abstract

Systemic administration of selective serotonin reuptake inhibitors (SSRIs)elicits larger increases in serotonin (5-HT) in raphe than in forebrain sites. Because serotonergic neuronal activity is suppressed, the mechanism underlying SSRI-induced increases in extracellular 5-HT is unclear. This study determined whether local infusion of SSRIs also elicited regionally selective increases in extracellular 5-HT, and whether changes depended on serotonergic neuronal depolarization. Conventional microdialysis methods were used to measure 5-HT in dorsal raphe (DRN), median raphe, nucleus accumbens (NAcc), and frontal cortex of unanesthetized rats. During infusion of SSRIs into each site, the maximum response was an similar to 6- to 7-fold increase in 5-HT in NAcc and frontal cortex, and an similar to 20-fold increase inDRN and median raphe. The larger increase in 5-HT in raphe was confirmed using zero-net-flux microdialysis. In NAcc, baseline 5-HT was 0.7 nM, and levels increased to a maximum of 3.1 nM during infusion of the SSRI citalopram. Baseline 5-HT in DRN was greater, 1.3 nM, and increased to 12.4 nM in response to citalopram. Consistent with evidence that autoreceptor activationinhibits serotonergic neuronal discharge, SSRI infusion into DRN produced a moderate decrease in 5-HT in NAcc. However, increases in 5-HT in DRN elicited by SSRI infusion were attenuated by 8-hydroxydipropylaminotetralin andtetrodotoxin. These data indicate that depolarization-dependent 5-HT release was not fully inhibited during SSRI infusion into DRN. In summary, SSRIsproduce larger increases in extracellular 5-HT in raphe than in forebrain sites. Increases depend in part on depolarization-induced release, which may be greater in raphe than in forebrain.

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Documento generato il 01/04/20 alle ore 22:52:38