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

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 dorsalraphe nucleus (DR) using microdialysis. 5-HT and NA concentrations in DR dialysates were virtually suppressed by TTX and increased by veratridine. The localand systemic administration of the α1aradrenoceptor antagonist prazosin reduced the DR 5-HT output but not that of NA. The maximal5-HT reduction induced by localprazosin administration (—78% at 100 μM) was more marked than by its systemic administration (—43% at 0.3 mg/kg). The localapplication of NA and desipramine, to increase the tone on DR aradrenoceptors, 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 a2-adrenoceptors on NA elements. Moreover, the systemic effect of clonidine on 5-HT (but not NA) was cancelled by lesion of the lateralhabenula and by anesthesia, and was slightly enhanced by corticaltransection. These data support the view that α1aradrenoceptors in the DRtonically 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 distalcontrolof 5-HT neurons. © 2003 Nature Publishing Group.