|
|
Contents
|
The parabrachial nucleus (PBN), an integrative site for the autonomic nervous system in the brainstem, is a target of neurons mediating cold information in the spinal dorsal horn. Many Fos-positive cells are observed in the PBN during cold exposure. These findings suggest the involvement of parabrachial neurons in the thermoregulatory system to maintain the body temperature in a cold environment. Thus, to test this possibility we investigated the effects of electrical stimulation of the PBN on O2 consumption (VO2) and those of electrolytic lesions of these regions on cold-induced thermogenesis. For stimulation experiments, male Wistar rats were anesthetized with urethan (1.2 g/kg, i.p.) and kept on a heating pad to maintain their body temperature at 36-37°C. A concentric electrode was stereotaxically inserted into the unilateral PBN region. Stimuli were 20 Hz monophasic square pulses with a duration of 0.5 ms and a strength of 10-40 μA for 5 min. VO2 was measured by an open-circuit method. After the experiments, the stimulation site was verified histologically on the coronal section of the brain. Electrical stimulation of the PBN (20 μA) immediately increased VO2 by 1.26 ± 0.11ml/min/kg0.75 (n=4) within 5 min, and VO2 returned to the baseline level within 25 min. The magnitude of thermogenesis increased with the intensity of the stimulus (10-40 μA). The effective site was located in and around the medial or lateral PBN. For lesion experiments, a monopolar stainless-steel electrode was inserted into the PBN under anesthesia with ketamine (50 mg/kg, i.p.) and 1% isoflurane in air. A battery-operated transmitter was implanted intraperitoneally in each rat to measure body temperature (Tb) and locomotor activity by a telemetry system. The measurement was performed at least 1 wk after the surgery. After the experiments, rats were anesthetized with Nembutal (50 mg/kg, i.p.) and the brain was fixed in formalin solution. The site and extension of lesion was examined histologically. Rats were placed in a metabolic chamber at the ambient temperature of 28.5 ± 0.1°C. The chamber was then cooled to 16.6 ± 0.6°C within 40 min and maintained at this temperature for 90 min. In rats with bilateral lesions in the PBN, cold stimulation elicited an integrated increase in VO2 of 429.3 ± 40.5 ml/kg0.75 (n=11), which was significantly smaller than that elicited in the sham rats (679.6 ± 35.0 ml/kg0.75, n=7). Cold exposure had no effect on Tb of sham-operated rats but decreased that of PBN-lesioned rats by 2.14 ± 0.12°C (n=11). Both frequency and duration of locomotor activity during the cold exposure were similar between the PBN-lesioned and sham-operated rats. The present study showed that electrical stimulation of the PBN elicited thermogenesis and that lesions in the PBN attenuated the thermogenesis during the cold exposure and resulted in a marked hypothermia. Accordingly, the PBN is involved in the neural mechanism of heat production against a cold exposure.