The role of 5-hydroxytryptamine in the regulation of sympathetic nerve discharge

Abstract

A large amount of evidence has accumulated to indicate that central serotonergic (5-hydroxytryptamine, 5-HT) neurons participate in the regulation of sympathetic nerve discharge (SND) and, therefore, blood pressure. Areas of the brain stem and spinal cord involved in vasomotor control are heavily innervated by 5-HT neurons [1, 2]. The area of the midline medulla that contains 5-HT neurons which project to autonomic nuclei corresponds to the classic medullary depressor region [3]. The close association between 5-HT descending neurons and midline sites that elicit vasodepressor responses when electrically stimulated has led to the conclusion that descending 5-HT medullospinal pathways inhibit sympathetic preganglionic neurons [4–7]. The findings that stimulation of presumed 5-HT-containing axons in the dorsolateral funiculus of the spinal cord inhibits sympathetic activity supports this hypothesis [8]. Early pharmacological studies based on the effects of 5-HT precursors and synthesis inhibitors support the concept that 5-HT neurons normally inhibit transmission in central sympathetic pathways. For example, administration of the 5-HT precursor 5-hydroxytryptophan results in a decrease in mean arterial blood pressure (MAP), heart rate (HR) and SND [9]. Furthermore, precursor administration produces a dose-dependent depression of spinal sympathetic reflexes. Taken together, these data suggest that central 5-HT neurons inhibit sympathetic neurons. However, a great deal of data generated in our laboratory suggests that 5-HT neurons excite rather than inhibit sympathetic neurons in the central nervous system. This chapter is intended to review this data with particular emphasis paid to the type of 5-HT receptor subtypes involved in the regulation of sympathetic neurons.