Miyamoto M, Narumi S, Nagai Y, Shima T, Nagawa Y
Jpn J Pharmacol. 1979 Jun;29(3):335-47. doi: 10.1254/jjp.29.335.
The mechanism of stimulatory action of thyrotropin-releasing hormone (TRH) on spontaneous motor activity was investigated in rats. TRH produced a significant hyperactivity with intraperitoneal administration of 20 mg/kg or bilateral injection of 10 micrograms into the nucleus accumbens septi (NAS). Following bilateral injection of 6-hydroxydopamine into the mesolimbic dopamine (DA) pathway, the hyperactivity induced by TRH was not altered, whereas the response to apomorphine given intraperitoneally or DA injected into the NAS was clearly enhanced. The TRH-induced hyperactivity was remarkably suppressed by alpha-methyltyrosine and in contrast, augmented by pargyline. Systemic injection of aminooxyacetic acid in a dose producing behavioral depression reduced markedly the TRH-induced hyperactivity. Bilateral injection of ethanolamine O-sulphate (100 micrograms) into the NAS produced no behavioral depression per se, but remarkably attenuated the hyperactivity response to TRH or DA (20 micrograms) given intraperitoneally or into the NAS. Both TRH (10(-5) and 10(-4) M) and methamphetamine (10(-6)--10(-4) M increased the spontaneous release of 14C-DA from rat NAS slices. These findings suggest that TRH induces hyperactivity by enhancing DA release from nerve terminals in the NAS without a direct stimulation of the post-synaptic DA recptors. TRH and GABA, independently or via interaction between them, may play a reciprocal regulatory role in the activity of the mesolimbic DA system.
研究了促甲状腺激素释放激素（TRH）对大鼠自发运动活动的刺激作用机制。腹腔注射20mg/kg或双侧伏隔核（NAS）注射10μg的TRH可产生显著的多动。在中脑边缘多巴胺（DA）通路双侧注射6-羟基多巴胺后，TRH诱导的多动没有改变，而腹腔注射阿扑吗啡或向NAS注射DA的反应明显增强。α-甲基酪氨酸可显著抑制TRH诱导的多动，相反，帕吉林可增强该反应。全身注射产生行为抑制作用剂量的氨氧乙酸可显著降低TRH诱导的多动。双侧向NAS注射硫酸乙醇胺（100μg）本身不会产生行为抑制，但可显著减弱腹腔注射或向NAS注射TRH或DA（20μg）所引起的多动反应。TRH（10⁻⁵和10⁻⁴M）和甲基苯丙胺（10⁻⁶ - 10⁻⁴M）均可增加大鼠NAS切片中¹⁴C-DA的自发释放。这些发现表明，TRH通过增强NAS中神经末梢的DA释放来诱导多动，而不是直接刺激突触后DA受体。TRH和GABA可能独立地或通过它们之间的相互作用，在中脑边缘DA系统的活动中发挥相互调节作用。
