[alpha]2-Adrenoceptor modulation of 5-HT biosynthesis in the rat brain

Abstract

The purpose of the present study is to clarify the modulation of the biosynthesis of serotonin (5-HT) via the [alpha]2-adrenoceptors in the brain. For this purpose. 5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system in the presence of the inhibition of aromatic -amino acid decarboxylase. Administration of [alpha]2-adrenoceptor agonist, clonidine, produced a reduction of the in vivo 5-HTP accumulation in the rat hippocampus and dorsal raphe nucleus. In addition, [alpha]2-adrenoceptor antagonist, idazoxan, increased the 5-HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine, clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased significantly. Brain tryptophan levels were unaffected by either clonidine or idazoxan. These results suggest that [alpha]2-adrenoceptors might modulate serotonin biosynthesis and this modulation might be related to the neuroanatomical differences in the rat brain.