BLOCKADE OF 5-HT2A RECEPTORS SUPPRESSES HYPERTHERMIC BUT NOT CARDIOVASCULAR RESPONSES TO PSYCHOSOCIAL STRESS IN RATS

The aim of this study was to determine whether 5-HT2A receptors mediate cardiovascular and thermogenic responses to acute psychological stresses. For this purpose, adult male Wistar hooded rats instrumented for telemetric recordings of either electrocardiogram (ECG) (n=12) or arterial pressure (n=12) were subjected, on different days, to four 15-min episodes of social defeat. Prior to stress, animals received s.c. injection of the selective 5-HT2A receptor antagonist SR-46349B (trans-4-((3Z)3-[(2-dimethylaminoethyl) oxyiminol-3-(2-fluorophenyl)propen-1-yl)-phenol, hemifumarate) (at doses of 0.3, 1.0 and 3.0 mg/kg) or vehicle. The drug had no effect on basal heart rate or heart rate variability indexes, arterial pressure, and core body temperature. Social defeat elicited significant and substantial tachycardic (347 7 to 500 +/- 7 bpm), pressor (77 +/- 4 to 97 +/- 4 mm Hg) and hyperthermic (37.0 +/- 0.3 to 38.5 +/- 0.1 degrees C) responses. Blockade of 5-HT2A receptors, at all closes of the antagonist, completely prevented stress-induced hyperthermia. In contrast, stress-induced cardiovascular responses were not affected by the blockade (except small reduction of tachycardia by the highest dose of the drug). We conclude that in rats, 5-HT2A receptors mediate stress-induced hyperthermic responses, but are not involved in the genesis of stress-induced rises in heart rate or arterial pressure, and do not participate in cardiovascular control at rest. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.