Narumi S, Nagawa Y
Adv Biochem Psychopharmacol. 1983;36:185-97.
TRH may act on the brain independently of its effects on the pituitary, and some of the CNS actions of TRH are probably closely related to brain catecholamines. TRH enhanced SMA by systemic injection (20 mg/kg, i.p.) or direct microinjection (10 micrograms) of TRH into the nucleus accumbens (ACB), one of the nerve terminal sites of the mesolimbic dopaminergic system, in rats. Prevention of this TRH effect by pretreatment with haloperidol or pimozide, a DA receptor blocker, or alpha-MT, an inhibitor of tyrosine hydroxylase, indicated that the SMA stimulatory action of TRH was the result of an enhancement of the release of DA from the nerve terminals. In rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH given i.p. (100 mg/kg) or into the nonlesioned caudate nucleus (50 micrograms) produced a circling toward the lesioned side which was suppressed by haloperidol or alpha-MT. The in vitro study demonstrated that TRH (5 X 10(-4)M) enhanced the release of preloaded [3H]DA from the slices of ACB after stable spontaneous DA release was established under superfusion, while a higher concentration (10(-2)M) was required to enhance the DA release from striatal slices. These in vitro studies supported the findings in investigation in vivo. In addition, TRH (2.5-20 mg/kg) markedly enhanced the circling behavior induced by L-DOPA or apomorphine in mice with unilateral caudate nucleus lesions induced by injection of 6-OHDA. In the 6-OHDA lesioned mice treated with TRH, DA-induced cyclic AMP formation was clearly enhanced in the striatal slices taken from the lesioned side but not from the intact side. In conclusion, TRH in low doses facilitates the DA presynaptic transmission by increasing the release of this amine from the ACB and also the DA postsynaptic transmission by increasing DA-stimulated cyclic AMP formation in striatum supersensitized with 6-OHDA. Endogenous TRH may play a physiological role as a modulator on DA transmission in CNS.
促甲状腺激素释放激素（TRH）可能独立于其对垂体的作用而作用于大脑，TRH的一些中枢神经系统作用可能与脑儿茶酚胺密切相关。在大鼠中，通过全身注射（20毫克/千克，腹腔注射）或直接微量注射（10微克）TRH到伏隔核（ACB）（中脑边缘多巴胺能系统的神经终末部位之一），TRH增强了自发运动活动（SMA）。用氟哌啶醇或匹莫齐特（一种多巴胺受体阻滞剂）或α-甲基酪氨酸（酪氨酸羟化酶抑制剂）预处理可预防这种TRH效应，这表明TRH对SMA的刺激作用是神经末梢多巴胺释放增加的结果。在经6-羟基多巴胺（6-OHDA）单侧损伤黑质纹状体多巴胺通路的大鼠中，腹腔注射高剂量TRH（100毫克/千克）或注射到未损伤的尾状核（50微克）会导致向损伤侧旋转，这种旋转被氟哌啶醇或α-甲基酪氨酸抑制。体外研究表明，在超灌流建立稳定的自发多巴胺释放后，TRH（5×10⁻⁴摩尔/升）可增强伏隔核切片中预加载的[³H]多巴胺的释放，而从纹状体切片中释放多巴胺则需要更高的浓度（10⁻²摩尔/升）。这些体外研究支持了体内研究的结果。此外，TRH（2.5 - 20毫克/千克）显著增强了由左旋多巴或阿扑吗啡诱导的、经6-OHDA注射造成单侧尾状核损伤的小鼠的旋转行为。在用TRH治疗的6-OHDA损伤小鼠中，损伤侧纹状体切片中多巴胺诱导的环磷酸腺苷（cAMP）形成明显增强，而完整侧则未增强。总之，低剂量的TRH通过增加ACB中这种胺的释放促进多巴胺突触前传递，还通过增加6-OHDA超敏化纹状体中多巴胺刺激的cAMP形成促进多巴胺突触后传递。内源性TRH可能作为中枢神经系统中多巴胺传递的调节剂发挥生理作用。
