We assessed the role of the Toll-like receptor 4 (TLR4) gene in the ventrolateral periaqueductal gray (vlPAG) region of morphine-dependent rats on attenuating withdrawal syndrome, and regulating glutamic acid decarboxylase (GAD67), glutamic acid (Glu), and gamma-aminobutyric acid (GABA). After siRNA-mediated downregulation of TLR4, changes were observed in withdrawal behavior and downstream signaling molecules. Rats were injected into the vlPAG with TLR4 siRNA, followed by intraperitoneal injection of morphine for 5 consecutive days, and then naloxone, and the behavioral indices of morphine withdrawal were observed. 'Wet-dog' shakes, teeth chattering, and the total scores of withdrawal reactions were reduced. TLR4 expression and Glu levels were reduced, whereas GAD67 and GABA levels were increased. Overall, these findings indicate that modifying TLR4 gene expression in the vlPAG stimulates expression of the downstream signaling molecule, GAD67, which decreases Glu levels and increases GABA levels. This mechanism may explain the inhibition of withdrawal syndrome in morphine-dependent rats.

中文翻译：

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Toll样受体4 siRNA注入腹侧导水管周围的灰色减弱了吗啡依赖性大鼠的戒断综合征。

我们评估了吗啡依赖大鼠的腹侧导水管周围灰色（vlPAG）区中Toll样受体4（TLR4）基因在减轻戒断综合征，调节谷氨酸脱羧酶（GAD67），谷氨酸（Glu）和γ-氨基丁酸（GABA）。siRNA介导的TLR4下调后，在戒断行为和下游信号分子中观察到变化。将大鼠用TLR4 siRNA注射到vlPAG中，然后连续5天腹膜内注射吗啡，然后再用纳洛酮，观察吗啡戒断的行为指标。“湿狗”摇动，牙齿颤抖和戒断反应的总得分降低了。TLR4表达和Glu水平降低，而GAD67和GABA水平升高。全面的，这些发现表明，修饰vlPAG中的TLR4基因表达会刺激下游信号分子GAD67的表达，从而降低Glu水平并增加GABA水平。这种机制可以解释吗啡依赖大鼠戒断综合征的抑制作用。