5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature.
The Journal of pharmacology and experimental therapeutics November 1, 2018 Mami Nakamura, Kaori Shintani-Ishida, Hiroshi Ikegaya
The recreational drug 25B-NBOMe, a selective agonist of the 5-HT2A receptor, induces hyperthermia only when the ambient temperature is high. In experiments on male rats, administration at 23°C did not change core body temperature, but at 29°C it caused significant hyperthermia 30–120 minutes later. The hyperthermia involves two mechanisms: peripheral vasoconstriction (indicated by a temporary drop in tail temperature) that stores heat, and thermogenesis in brown adipose tissue (BAT) that begins 60–120 minutes after administration. Blocking peripheral 5-HT2A receptors with sarpogrelate suppressed the hyperthermia, while destroying central neurons did not. Plasma serotonin levels decreased at 29°C, and giving serotonin partially suppressed the hyperthermia, suggesting that reduced peripheral serotonin triggers BAT thermogenesis. Peripheral serotonin thus plays a partial but important role in thermoregulation.