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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/33047
Title: In vivo efflux of serotonin in the dorsal raphe nucleus of 5-HT1A receptor knockout mice
Authors: Bortolozzi, Analía ; Amargós-Bosch, Mercè; Toth, Miklos; Artigas, Francesc ; Adell, Albert
Keywords: dorsal raphe nucleus
5-HT1A receptor knockout mice
5-HT1B receptors
Issue Date: Mar-2004
Publisher: Wiley-Blackwell
Citation: Journal of Neurochemistry 88 (6) :1373-1379 (2004)
Abstract: In the dorsal raphe nucleus (DR), extracellular serotonin (5-HT) regulates serotonergic transmission through 5-HT1A autoreceptors. In this work we used in vivo microdialysis to examine the effects of stressful and pharmacological challenges on DR 5-HT efflux in 5-HT1A receptor knockout (5-HT1A-/-) mice and their wild-type counterparts (5-HT1A+/+). Baseline 5-HT concentrations did not differ between both lines of mice, which is consistent with a lack of tonic control of 5-HT1A autoreceptors on DR 5-HT release. (R)-(+)-8-Hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT, 0.5 mg/kg) reduced 5-HT levels to 30% of basal values in 5-HT1A+/+ mice, but not in 5-HT1A-/- mice. The selective 5-HT1B receptor agonist 1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5H-pyrrolo[3,2-b]pyridin-5-one dihydrochloride (CP 93129, 300 micro m) reduced dialysate 5-HT to the same extent (30-40% of baseline) in the two genotypes, which suggests a lack of compensatory changes in 5-HT1B receptors in the DR of such mutant mice. Both a saline injection and handling for 3 min increased DR dialysate 5-HT in mutants, but not in 5-HT1A+/+ mice. Fluoxetine (5 and 20 mg/kg) elevated 5-HT in a dose-dependent manner in both genotypes. However, this effect was markedly more pronounced in the 5-HT1A-/- mice. The increased responsiveness of the extracellular 5-HT in the DR of 5-HT1A receptor knockout mice reflects a lack of the autoinhibitory control exerted by 5-HT1A autoreceptors.
Publisher version (URL): http://onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.2003.02267.x/pdf
URI: http://hdl.handle.net/10261/33047
DOI: 10.1046/j.1471-4159.2003.02267.x
ISSN: 0022-3042
E-ISSN: 1471-4159
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