Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, China.
Department of Pathogenic Biology, Chengdu Medical College, Chengdu, China.
Neurosci Lett. 2020 Sep 25;736:135283. doi: 10.1016/j.neulet.2020.135283. Epub 2020 Jul 30.
This study investigated the effects of minocycline microinjections, into the midbrain periaqueductal gray (PAG), on morphine withdrawal and the expression of pannexin-1 (panx1), phosphorylated mammalian target of rapamycin (p-mTOR), protein kinase A (PKA), and cAMP response element-binding protein (CREB). Rats were injected with morphine, intraperitoneally, at increasing doses, twice per day, to establish animal models of morphine exposure. Minocycline was administered into the PAG before the first intraperitoneal (i.p.) injection of morphine each day, on days 1-4. On the last day of the experiment, all rats were injected with naloxone, and morphine withdrawal was observed, and then changes in the expression levels of ionized calcium-binding adaptor molecule 1 (Iba1) and its downstream factors, panx1, p-mTOR, PKA, and CREB were evaluated by western blot and immunohistochemistry analyses. Morphine withdrawal increased microglial activation, whereas minocycline could inhibit microglial activation and withdrawal and the downregulation of panx1, p-mTOR, PKA, and CREB expression, reducing the effects of morphine withdrawal.
本研究探讨了将米诺环素微注射到中脑导水管周围灰质（PAG）中对吗啡戒断和连接蛋白-1（panx1）、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）、蛋白激酶 A（PKA）和 cAMP 反应元件结合蛋白（CREB）表达的影响。大鼠每天两次腹腔注射递增剂量的吗啡，以建立吗啡暴露的动物模型。米诺环素在每天第一次腹腔注射吗啡前注入 PAG，持续 4 天。在实验的最后一天，所有大鼠均注射纳洛酮，观察吗啡戒断，然后通过 Western blot 和免疫组织化学分析评估小胶质细胞活化的离子钙结合衔接分子 1（Iba1）及其下游因子 panx1、p-mTOR、PKA 和 CREB 的表达变化。吗啡戒断增加小胶质细胞活化，而米诺环素可抑制小胶质细胞活化和戒断以及 panx1、p-mTOR、PKA 和 CREB 表达的下调，从而减轻吗啡戒断的影响。
