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5-Hydroxytryptamine 1A receptors inhibit cold-induced sympathetically mediated cutaneous vasoconstriction in rabbits

Y. Ootsuka and W. W. Blessing

5-HT_1A receptor agonists lower body temperature. We have investigated whether activation of 5-HT_1A receptors inhibits cutaneous sympathetic discharge so that dilatation of the cutaneous vascular bed lowers body temperature by increasing heat transfer to the environment. We measured ear pinna blood flow in conscious rabbits (with chronically implanted Doppler ultrasound flow probes), and postganglionic sympathetic vasomotor nerve activity in anaesthetized rabbits. Recordings from conscious rabbits were made in a cage at 26 °C and the rabbit was then transferred to a cage at 10 °C. The ear pinna Doppler signal fell from 56 ± 4 cm s^-1 in the 26 °C cage to 4 ± 1 cm s^-1 (P < 0.0001, n = 24) after 30 min in the 10 °C cage, and body temperature increased from 38.8 ± 0.2 to 39.0 ± 0.2 °C (P < 0.01, n = 24). The 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg kg^-1 I.V.) reversed the cold-induced fall in ear pinna blood flow (Doppler signal increased from 5 ± 1 to 55 ± 8 cm s^-1, P < 0.001, n = 7) within 5 min when administered 30 min after transfer to the 10 °C cage, and prevented the fall in ear pinna blood flow when administered before the rabbit was transferred to the 10 °C cage. Body temperature decreased after administration of 8-OH-DPAT. These changes were abolished by the specific 5-HT_1A antagonist WAY-100635 (0.1 mg kg^-1 I.V.). In anaesthetized rabbits, 8-OH-DPAT (0.1 mg kg^-1 I.V.) reduced resting postganglionic cutaneous sympathetic vasomotor discharge, and prevented the increase normally elicited by cooling the trunk. Our experiments constitute the first demonstration that activation of 5-HT_1A receptors powerfully inhibits cold-induced increases in cutaneous sympathetic vasomotor discharge, thereby dilating the cutaneous vascular bed and increasing transfer of heat to the environment.

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