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

双侧下丘脑视前区微量注射GABAA(300 mM，100nL)或GABA_A受体激动剂Muscimol(100μM，100nL)均可增加乌拉坦-氯醛糖麻醉的人工呼吸机大鼠的全身耗氧率和体心(结肠)温度。GABA诱导的发热伴随着心动过速反应和股骨或颈部肌肉的肌电活动。肌松药(潘库溴铵1 mg/kg+维库溴铵4 mg/kg，静脉注射)抑制GABA诱导的肌电活动，但对GABA诱导的产热无明显影响。但预先注射β肾上腺素能受体心得安(5 mg/kg，iv)。显著减轻GABA引起的VO2增加和心动过速反应。因此，GABA诱导的VO2增加主要反映了非颤抖的产热作用。另一方面，通过接触一个装有28℃水的塑料袋来冷却大鼠剃毛的背部，也会引起发热、心动过速和肌电反应。双侧POA内微量注射GABA_A受体拮抗剂荷包牡丹碱(500μM，100nL)，但不注射生理盐水，可阻断皮肤降温引起的上述反应。这些结果表明，冷诱导的产热需要POA中的GABA和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.