Selective blockade of 5‐HT2A receptors suppresses hyperthermic but not cardiovascular responses elicited by social defeat in rats

Abstract

Our aim was to determine whether 5‐HT2A receptors are involved in mediating autonomic responses to psychological stress. For this purpose, using telemetry, we assessed changes in the heart rate, arterial pressure and core body temperature elicited in Wistar rats during social defeat. Fifteen min prior to entering the resident's cage, intruders received s.c. injection of either selective 5‐HT2A receptor antagonist SR‐46379B (0.3, 1.0 or 3.0 mg/kg) or vehicle. After vehicle, social defeat induced substantial hyperthermic (+1.1±0.1°C), tachycardic (+142±11 bpm) and pressor (+22±3 mmHg) responses. SR46349B at doses 0.3 and 1.0 mg/kg abolished hyperthermia, and at the dose of 3.0 mg kg reverted it to the hyporthermia (−0.41±0.1°C; n=7, p<0.01 for all doses). The drug reduced tachycardia (to +115±13 bpm, n=15, p<0.05) only when applied at the highest dose, and did not affect pressor response at any dose (n=8). Anti‐hyperthermic effect was still well expressed 1.5 h after injection, whereas anti‐tachycardic effect waned at the end of defeat (30 min after injection). We conclude that activation of 5‐HT2A receptors is essential for the expression of stress‐induced hyperthermia, that contribution of these receptors to the stress‐induced tachycardia is minor, and that they do not mediate rise in arterial pressure during stress.