Selective blockade of 5-HT2A receptors attenuates the increased temperature response in brown adipose tissue to restraint stress in rats

Abstract

Previous studies have demonstrated that 5-HT2A receptors may be involved in the central control of thermoregulation and of the cardiovascular system. Our aim was to test whether these receptors mediate thermogenic and tachycardiac responses induced by acute psychological stress. Three groups of adult male Hooded Wistar rats were instrumented with: (i) a thermistor in the interscapular area (for recording brown adipose tissue temperature) and an ultrasound Doppler probe (to record tail blood flow); (ii) temperature dataloggers to record core body temperature; (iii) ECG electrodes. On the day of the experiment, rats were subjected to a 30-min restraint stress preceded by s.c. injection of either vehicle or SR-46349B (a serotonin 2A receptor antagonist) at doses of 0.01, 0.1 and 1.0 mg/kg. The restraint stress caused a rise in brown adipose tissue temperature (from, mean +/- s.e.m., 36.6 +/- 0.2 to 38.0 +/- 0.2 degrees C), transient cutaneous vasoconstriction (tail blood flow decreased from 12 +/- 2 to 5 +/- 1 cm/s), increase in heart rate (from 303 +/- 15 to 453 +/- 15 bpm at the peak, then reduced to 393 +/- 12 bpm at the steady state), and defaecation (6 +/- 1 pellets per restraint session). The core body temperature was not affected by the restraint. Blockade of 5-HT2A receptors attenuated the increase in brown adipose tissue temperature and transient cutaneous vasoconstriction, but not tachycardia and defaecation elicited by restraint stress. These results indicate that psychological stress causes activation of 5-HT2A receptors in neural pathways that control thermogenesis in the brown adipose tissue and facilitate cutaneous vasoconstriction.

Effect of physical restraint on the limits of thermoregulation in telemetered rats

“…Restraint in rodents clearly elicits an adrenergic, hypermetabolic response (Nagasaka et al 1979). Ootsuka et al (2008) found a marked rise in temperature of the interscapular brown adipose tissue during physical restraint. This would suggest that restraint-induced activation of thermogenesis in brown adipose tissue contributes to the overall rise in core temperature.…”

“…Ootsuka et al (2008) made continuous measurements of tail blood flow in rats subjected to 30 min of physical restraint and found a transient reduction when first placed in the restrainer, followed by recovery and elevation in blood flow after about 20 min of restraint. We cannot reconcile a rise in total tail blood flow and reduction in the HLI from the tail observed in the present study.…”

“…The hyperthermic response at standard laboratory temperatures is thought to be a result of the stress-induced increase in metabolic heat production. A transient reduction in tail blood flow may also contribute to the rise in core temperature during restraint (Ootsuka et al 2008). Moreover, restraint stress at a temperature of ∼22…”

“…It has been recognized for many years that the thermoregulatory and cardiovascular systems of rats are compromised during physical restraint (Nagasaka et al 1979;Thornhill et al 1979;Gordon, 1993;Ootsuka et al 2008). When restrained at standard room temperatures (i.e.…”

Nonshivering thermogenesis without interscapular brown adipose tissue involvement during conditioned fear in the rat

“…Shibata and Nagasaka (25) used a subtraction method similar to ours to estimate iBAT thermogenesis and demonstrated that the increase they observed after a 2-min immobilization was abolished by sympathectomy. Ootsuka et al (23) used a more common restraint paradigm that lasted 30 min; however, body temperature was not subtracted, and no propranolol injection or sympathectomy was made to verify the iBAT origin of the local temperature increase. Clearly, further work is needed to clarify the role of BAT in the hyperthermic response of different forms of psychological stress.…”