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Título

Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors

AutorBortolozzi, Analía CSIC ORCID; Artigas, Francesc CSIC ORCID
Palabras clave5-hydroxytryptamine
α-adrenoceptors
Dorsal raphe nucleus
Frontal cortex
Habenula
Noradrenaline
Fecha de publicaciónmar-2003
EditorNature Publishing Group
CitaciónNeuropsychopharmacology 28 (3) : 421-434 (2003)
ResumenThe interactions between the brainstem serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic (NA) systems are important for the pathophysiology and treatment of affective disorders. We examined the influence of -adrenoceptors on 5-HT and NA release in the rat dorsal raphe nucleus (DR) using microdialysis. 5-HT and NA concentrations in DR dialysates were virtually suppressed by TTX and increased by veratridine. The local and systemic administration of the 1-adrenoceptor antagonist prazosin reduced the DR 5-HT output but not that of NA. The maximal 5-HT reduction induced by local prazosin administration (-78% at 100 M) was more marked than by its systemic administration (-43% at 0.3 mg/kg). The local application of NA and desipramine, to increase the tone on DR 1-adrenoceptors, did not enhance 5-HT release. The local (100 M) or systemic (0.1–1 mg/kg s.c.) administration of clonidine reduced 5-HT and NA release (-48 and -79%, respectively, at 1 mg/kg), an effect reversed by RX-821002, which by itself increased both amines when given systemically. DSP-4 pretreatment prevented the effects of clonidine on 5-HT, suggesting the participation of 2-adrenoceptors on NA elements. Moreover, the systemic effect of clonidine on 5-HT (but not NA) was cancelled by lesion of the lateral habenula and by anesthesia, and was slightly enhanced by cortical transection. These data support the view that 1-adrenoceptors in the DR tonically stimulate 5-HT release, possibly at nearly maximal tone. Likewise, the 5-HT release is modulated by 2-adrenoceptors in NA neurons and in forebrain areas involved in the distal control of 5-HT neurons.
Versión del editorhttp://dx.doi.org/10.1038/sj.npp.1300061
URIhttp://hdl.handle.net/10261/34692
DOI10.1038/sj.npp.1300061
ISSN0893-133X
E-ISSN1740-634X
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