In both conscious and anesthetized rabbits, we determined whether microinjection of a 5-hydroxytryptamine (5-HT) 1A receptor agonist 8-hydroxy-2-(di-n-propylaminio) tetralin (8-OH-DPAT) into the medullary raphé/parapyramidal region inhibits thermoregulatory vasoconstriction and whether microinjection of a 5-HT1A receptor antagonist (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (WAY-100635) into the raphé reverses the cutaneous vasomotor changes induced by intravenous administration of 8-OH-DPAT. In conscious rabbits with measuring ear pinna blood flow, after microinjection of 8-OH-DPAT (3-5 nmol in 300-500 nl) into the raphé, transferring the animal from a warm cage (25-28 degrees C) to a cold cage (5-10 degrees C) did not reduce the ear pinna flow (from 57 +/- 7 cm/s to 59 +/- 3 cm/s, P > 0.05, n = 5), unlike Ringer-treated animals. Microinjection of WAY-100635 (5 nmol in 500 nl) into the raphé reversed ear pinna flow changes induced by intravenous administration of 8-OH-DPAT (0.1 mg/kg, i.v.). In anesthetized rabbits with measuring postganglionic ear pinna sympathetic nerve activity, microinjection of 8-OH-DPAT (1-2 nmol in 100-200 nl) into the raphé reduced resting ear pinna sympathetic nerve activity to 14 +/- 4% of pre-injection level (P < 0.01, n = 12) and attenuated increases in ear pinna sympathetic nerve activity normally elicited by cooling the animal's trunk. WAY-100635 (2 nmol into 200 nl) into the raphé reversed inhibition of ear pinna sympathetic nerve activity elicited by 8-OH-DPAT (0.1 mg/kg, i.v.). The activation of 5-HT1A receptors expressed on the medullary raphé neurons results in reversal of cold-elicited cutaneous vasoconstriction possibly through inhibition of sympathetic premotor neurons that innervate sympathetic preganglionic neurons controlling cutaneous vasomotion.