Blockade of 5-HT2A receptors suppresses hyperthermic but not cardiovascular responses to psychosocial stress in rats

• Published in: Neuroscience 2009-03, Vol.159 (3), p.1185-1191
• Main Authors: Beig, M.I, Baumert, M, Walker, F.R, Day, T.A, Nalivaiko, E
• Format: Article
• Language: English
• Subjects: 5-HT; Analysis of Variance; Animals; arterial pressure; Biological and medical sciences; Blood Pressure - drug effects; Body Temperature - drug effects; Cardiovascular System - drug effects; Cardiovascular System - physiopathology; core body temperature; Electrocardiography; Fever - drug therapy; Fever - physiopathology; Fluorobenzenes - administration & dosage; Fluorobenzenes - pharmacology; Fundamental and applied biological sciences. Psychology; heart rate; Heart Rate - drug effects; Male; Neurology; Phenols - administration & dosage; Phenols - pharmacology; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A - metabolism; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists - administration & dosage; Serotonin Antagonists - pharmacology; social defeat; Social Dominance; Stress, Psychological - drug therapy; Stress, Psychological - physiopathology; Tachycardia - drug therapy; Tachycardia - physiopathology; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.01.038

Abstract 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)oxyimino]-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 °C) responses. Blockade of 5-HT2A receptors, at all doses 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.