Cold-induced thermogenesis requires GABA in the preoptic area of the hypothalamus

双侧向下丘脑视前区（POA）微注射GABA （300 mM, 100 nl）或GABA_A受体激动剂muscimol （100 μM, 100 nl）可提高人工通气麻醉大鼠的全身耗氧量（VO2）和体核（结肠）温度。gaba诱导的产热伴随着心动过速反应和股骨或颈部肌肉肌电图（EMG）活动记录。肌肉松弛剂预处理（1 mg/kg泮库溴铵加4 mg/kg维库溴铵，静脉注射）可阻止gaba诱导的肌电活动，但对gaba诱导的生热作用无显著影响。然而，用β-肾上腺素能素普萘洛尔（5mg /kg，静脉注射）预处理可显著减弱gaba诱导的VO2升高和心动过速反应。因此，gaba诱导的VO2增加主要反映了非寒战产热。另一方面，通过接触装有28℃水的塑料袋来冷却大鼠剃光的背部也会引起产热、心动过速和肌电反应。双侧微注射GABA_A受体拮抗剂双管碱（500 μM, 100 nl），但不注射生理盐水，可阻断这些皮肤冷却诱导的反应。这些结果表明，冷诱导产热需要GABA和POA中的GABA_A受体。

Bilateral microinjections of GABA (300 mM, 100 nl) or the GABA_A receptor agonist muscimol (100 μM, 100 nl) into the preoptic area (POA) of the hypothalamus increased both the rate of whole-body oxygen consumption (VO2) and the body core (colonic) temperature of urethane-chloralose-anesthetized, artificially ventilated rats. The GABA-induced thermogenesis was accompanied by a tachycardic response and electromyographic (EMG) activity recorded from the femoral or neck muscles. Pretreatment with muscle relaxants (1 mg/kg pancuronium bromide plus 4 mg/kg vecuronium bromide, I.V.) prevented the GABA-induced EMG activity but had no significant effect on the GABA-induced thermogenesis. However, pretreatment with the β-adrenoceptor propranolol (5 mg/kg, I.V.) greatly attenuated the GABA-induced increase in VO2 and tachycardic responses. Accordingly, the GABA-induced increase in VO2 reflected mainly nonshivering thermogenesis. On the other hand, cooling of the shaved back of the rat by contact with a plastic bag containing 28 ℃ water also elicited thermogenic, tachycardic, and EMG responses. Bilateral microinjections of the GABA_A receptor antagonist bicuculline (500 μM, 100 nl), but not those of vehicle saline, into the POA blocked these skin cooling-induced responses. These results suggest that cold-induced thermogenesis requires GABA and GABA_A receptors in the POA.