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

Figures & data

Figure 1 Restraint stress causes changes in the iBAT temperature (upper traces in each panel) and in the tail blood flow (bottom traces); both records are from the same rat on different days. In (A), vehicle was injected s.c. 15 min prior to the restraint; in (B), restraint was preceded by injection of SR-46349B at a high dose (1 mg/kg s.c.). SR-46349B attenuated the increase in iBAT temperature and the decrease in tail blood flow during restraint.

Figure 2 Blockade of 5-HT2A receptors with SR-46349B attenuates the stress-induced increase in iBAT temperature. Mean group data are expressed as delta values. (A) Averaged traces from 8 rats obtained after injection of either vehicle (○) or SR-46349B at a dose of 1 mg/kg (•) 15 min prior to the restraint. There was a significant difference (p < 0.01, n = 8) in the increase in iBAT temperature between vehicle and drug conditions. (B) mean values for stress-induced changes in the iBAT temperature for 4 different conditions (vehicle or SR-46349B at doses of 0.01, 0.1 and 1.0 mg/kg s.c.). **Significantly different, p < 0.01, respectively. Data are expressed as difference between basal (pre-injection) values and maximal temperature increases during restraint.

Figure 3 Blockade of 5-HT2A receptors with SR-46349B attenuates stress-induced transient decreases in tail blood flow. (A) averaged traces from 8 rats obtained after injection of either vehicle (○) or SR-46349B at a dose of 1 mg/kg (•) 15 min prior to the restraint. There was a significant difference between vehicle and drug conditions during the first 5 min of restraint (p < 0.01, n = 8). (B) Mean data values obtained during the baseline period (Bas) are compared to the mean data values obtained during the first 5 min of the restraint, for 4 different conditions (vehicle or SR-46349B at doses of 0.01, 0.1 and 1.0 mg/kg s.c.). Restraint provoked significant decreases in the tail blood flow only after vehicle and the low dose of the drug (* and ** significantly different, p < 0.05 and < 0.01, respectively).

Table I.  Effects of SR-46349B on the tail blood flow before and during restraint.

	Baseline	Pre-restraint	Restraint 0–5 min	Restraint 5–30 min
Vehicle	12.6 ± 1.7	− 2.4 ± 1.2	− 8.8 ± 2.1	+5.8 ± 3.4
SR-46349B 0.01 mg/kg	14.2 ± 2.6	− 2.9 ± 1.2	− 8.6 ± 1.6	+6.3 ± 2.2
SR-46349B 0.1 mg/kg	9.1 ± 1.3	+4.0 ± 1.0^##	+0.9 ± 1.2^##	+7.4 ± 1.2
SR-46349B 1.0 mg/kg	13.4 ± 2.3	+5.1 ± 1.6^##	− 1.3 ± 1.2^##	+4.7 ± 2.1

Baseline values were obtained prior to the drug or vehicle injections; pre-restraint values—after the injections but before the restraint. ^##p < 0.05, significantly different from the corresponding value in the vehicle-treated group. The two columns on the right present data obtained during 0–5 min and during the remainder of restraint, respectively. Baseline data are expressed as absolute values of blood velocity (cm/s); data during pre-restraint and restraint periods are presented as a difference between basal values and mean values during the corresponding period.

Figure 4 Core body temperature is not affected by SR-46349B nor by the restraint stress. Averaged traces from 7 rats obtained after injection of either vehicle (○) or SR-46349B at a dose of 1 mg/kg (•) 15 min prior to restraint. Two-way ANOVA did not reveal any significant effects of either treatment or restraint on the core body temperature.

Figure 5 Blockade of 5-HT receptors with SR-46349B does not affect tachycardia elicited by the restraint stress. Averaged traces from 7 rats obtained after injection of either vehicle (○) or SR-46349B at a dose of 1 mg/kg (•) 15 min prior to the restraint. Heart rate was significantly elevated following vehicle or drug injection and during restraint compared to the baseline. There was no significant effect of SR46349B.