Abstract
The 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 α-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 α1-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 μM) 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 α1-adrenoceptors, did not enhance 5-HT release. The local (100 μM) 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 α2-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 α1-adrenoceptors in the DR tonically stimulate 5-HT release, possibly at nearly maximal tone. Likewise, the 5-HT release is modulated by α2-adrenoceptors in NA neurons and in forebrain areas involved in the distal control of 5-HT neurons.
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Acknowledgements
This work was supported by grants from the Ministry of Science and Technology and Ministry of Health (SAF 2001–2133 and Fis 2001–1147). The authors wish to acknowledge the skilful technical assistance of Leticia Campa in the HPLC analyses. A.B. is recipient of a postdoctoral fellowship (MAE, Fundación Carolina).
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Bortolozzi, A., Artigas, F. Control of 5-Hydroxytryptamine Release in the Dorsal Raphe Nucleus by the Noradrenergic System in Rat Brain. Role of α-Adrenoceptors. Neuropsychopharmacol 28, 421–434 (2003). https://doi.org/10.1038/sj.npp.1300061
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