Ishiwata Takayuki, Saito Takehito, Hasegawa Hiroshi, Yazawa Toru, Kotani Yasunori, Otokawa Minoru, Aihara Yasutsugu
Department of Biology, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-ohsawa, Hachioji, Tokyo 192-0397, Japan.
Brain Res. 2005 Jun 28;1048(1-2):32-40. doi: 10.1016/j.brainres.2005.04.027.
Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.
γ-氨基丁酸（GABA）在前视区和下丘脑前部（PO/AH）的作用被认为与体温调节有关。然而，其在体温调节中的精确作用仍不清楚。此外，关于其在主动体温调节过程中在PO/AH的释放模式知之甚少。我们使用微透析和遥测技术，在正常（23摄氏度）、寒冷（5摄氏度）和炎热（35摄氏度）环境温度下，对自由活动大鼠进行GABA药理刺激期间，测量了几个与体温调节相关的参数。我们还结合微透析和高效液相色谱法（HPLC），测量了寒冷（5摄氏度）和热暴露（35摄氏度）期间PO/AH中的细胞外GABA水平。向PO/AH灌注GABA A激动剂蝇蕈醇会使体温升高，这与心率（HR）增加有关，心率增加作为所有环境温度下产热的指标。虽然作为散热指标的尾皮肤温度（T(tail)）仅在正常环境温度下升高，但其反应与HR和体温相比相对延迟，表明T(tail)的升高是对HR和体温升高的次级反应。在所有环境温度下，运动活动也会增加，但其反应并不异常。有趣的是，在每个环境温度下灌注GABA A拮抗剂荷包牡丹碱后，体温调节反应有所不同。在正常环境温度条件下，灌注荷包牡丹碱对任何参数均无影响。然而，在寒冷环境温度下，尽管活动亢进且T(tail)升高，但该操作仍会导致显著体温过低并伴有HR下降。在炎热环境温度条件下，它会导致体温过高并伴有HR升高，但T(tail)无额外变化。此外，寒冷暴露期间细胞外GABA水平显著升高。其释放在热暴露期间低于正常环境。这些结果表明，PO/AH中的GABA是寒冷环境温度下解除产热抑制和抑制散热的重要神经递质。它是炎热环境温度下抑制产热的神经递质。
