5-HT2 receptor agonists increase spontaneous sympathetic nerve discharge.

Area of Science:

• Neuropharmacology
• Autonomic Nervous System Research
• Cardiovascular Physiology

Background:

• Serotonin (5-HT) pathways are implicated in regulating sympathetic outflow.
• Understanding the specific 5-HT receptor subtypes involved is crucial for elucidating central sympathetic control mechanisms.

Purpose of the Study:

• To investigate the effects of the selective 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), on sympathetic nerve activity.
• To determine the role of 5-HT2 receptors in mediating DOI-induced sympathetic activation.

Main Methods:

• Sympathetic nerve discharge was recorded from the inferior cardiac nerve in chloralose-anesthetized cats.
• Intravenous administration of DOI at varying doses (0.01-1.0 mg/kg).
• Administration of 5-HT2 antagonists (ketanserin, LY 53857) and prazosin for reversal and blockade studies.

Main Results:

• DOI caused a dose-dependent, marked increase in sympathetic nerve discharge, reaching up to 1750% of control values.
• The DOI-induced increase in sympathetic activity was significantly reversed by ketanserin and LY 53857.
• Pretreatment with ketanserin, but not prazosin, completely prevented the sympathetic activation by DOI.

Conclusions:

• Selective activation of 5-HT2 receptors potently stimulates sympathetic nerve discharge.
• These findings support a significant role for serotonin, acting via 5-HT2 receptors, in the central regulation of sympathetic activity.
• 5-HT2 receptors are critical mediators of sympathetic outflow in the studied model.