Regulation of the release of 5-hydroxytryptamine in the median raphe nucleus of the rat by catecholaminergic afferents

The present study was conducted in order to examine the influence of catecholaminergic afferents on the release of serotonin in the median raphe nucleus in vivo. To this aim, selective dopamine D-1 and D-2, and alpha(1)- and alpha(2)-adrenergic agonists and antagonists were administered locally (1, 10 and 100 mu M) through a dialysis probe implanted in the median raphe nucleus of freely moving rats. The D-1 and D-2 agonists, (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF-38393) and quinpirole, respectively, and the D-1 and D-2 antagonists, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH-23390) and raclopride, respectively, did not alter the release of serotonin in the median raphe nucleus. The alpha(1)-adrenoceptor agonist phenylephrine did not modify the release of serotonin in this nucleus, although an increased release was observed when the more potent alpha(1)-adrenoceptor agonist cirazoline was used. In contrast, the alpha(1)-adrenoceptor antagonist prazosin reduced the release of 5-hydroxytryptamine (5-HT) in a concentration-dependent manner. The release of 5-HT was also reduced by the alpha(2)-adrenoceptor agonist clonidine and increased by the alpha(2)-adrenoceptor antagonist 2-methoxy-idazoxan (RX821002). These results indicate that the release of serotonin in the median raphe nucleus does not appear to be regulated by dopaminergic afferents through the activation of dopamine D-1 or D-2 receptors. On the contrary, it is suggested that endogenous noradrenaline exerts a direct tonic stimulatory control on the release of serotonin through alpha(1)-adrenoceptors, and an indirect tonic inhibitory influence through alpha(2)-adrenoceptors located probably in noradrenergic nerve terminals within the median raphe nucleus.