5-Hydroxytryptamine demonstrated immunohistochemically in rat cerebrovascular nerves largely represents 5-hydroxytryptamine uptake into sympathetic nerve fibres.

This study has re-examined, by immunohistochemistry, a proposed serotonergic innervation of major cerebral vessels in the rat. Previous studies had demonstrated a dense perivascular plexus of 5-hydroxytryptamine immunoreactive nerve fibres upon major cerebral vessels in this and many other species. The present work has shown, however, that 5-hydroxytryptamine immunoreactive nerve fibres are rarely observed in cerebral vessels prepared by perfusion-fixation in situ, and only form a well-developed plexus in vessels prepared, as in previous studies, by immersion-fixation. Prior treatment with a predominantly noradrenergic uptake inhibitor desmethylimipramine but not the serotonergic uptake inhibitor fluoxetine produced a major diminution in the 5-hydroxytryptamine immunoreactive plexus visualized in these immersion-fixed vessels. In addition, 5-hydroxytryptamine immunoreactive nerves were only occasionally observed in immersion-fixed vessels from animals that had been pretreated with 6-hydroxydopamine to produce adrenergic denervation. The removal, firstly, of vessel-contained blood, by left ventricular perfusion with Krebs' solution, prior to vessel dissection and immersion-fixation, resulted in an absence of 5-hydroxytryptamine immunoreactivity in perivascular nerves. Immunoreactivity could then be restored by briefly incubating vessels in Krebs' solution containing either blood or 5-hydroxytryptamine before fixation. It would appear therefore that 5-hydroxytryptamine is rarely present under normal circumstances in the perivascular nerves of major cerebral vessels, and that previous descriptions of a dense serotonergic nerve plexus represent 5-hydroxytryptamine in blood released during vessel dissection being taken up via the noradrenaline-uptake system into perivascular sympathetic nerves. The possibility is thus raised that 5-hydroxytryptamine uptake and interaction within perivascular adrenergic nerves could occur in those cerebrovascular disorders where blood is released.