Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China; Medical Faculty, Kunming University of Science and Technology, Kunming, 650500, China.
Medical Faculty, Kunming University of Science and Technology, Kunming, 650500, China.
Neuropharmacology. 2018 Dec;143:63-70. doi: 10.1016/j.neuropharm.2018.09.027. Epub 2018 Sep 18.
Morphine is widely used for clinical pain management and induces the dependence. Addiction to morphine is a major public health issue. Geranylgeranylacetone (GGA) is widely used in clinic for treating ulcer. GGA induces expression of thioredoxin-1 (Trx-1) extensively. Trx-1 is a redox regulating protein and plays protecting roles in nervous system. GGA prevents mice against morphine-induced hyperlocomotion, rewarding effect, and withdrawal syndrome. However, whether GGA blocks morphine-conditioned place preference (CPP) reinstatement is still unknown. In the present study, we found that GGA administration blocked the reinstatement of morphine-CPP. The expressions of Trx-1, N-methyl d-aspartate receptor 2B subunit (NR2B), phosphorylated Ca/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylated extracellular signaling regulated kinases (p-ERK), and phosphorylated cAMP-response element binding protein (p-CREB) were induced in nucleus accumbens (NAc) and hippocampus by morphine or GGA, whereas these proteins were not changed by morphine in GGA-treated mice. Our results indicate that GGA may prevent the reinstatement of morphine-CPP through strengthening the expression of Trx-1 and regulating NR2B/ERK pathway. Thus, we suggest that GGA may be a promising therapeutic candidate for morphine-induced relapse.
吗啡被广泛用于临床疼痛管理，并导致依赖性。吗啡成瘾是一个主要的公共卫生问题。金合欢基丙酮（GGA）广泛用于临床治疗溃疡。GGA 广泛诱导硫氧还蛋白-1（Trx-1）的表达。Trx-1 是一种氧化还原调节蛋白，在神经系统中发挥保护作用。GGA 可防止小鼠对吗啡诱导的过度活动、奖赏效应和戒断综合征。然而，GGA 是否阻断吗啡条件性位置偏爱（CPP）的复燃尚不清楚。在本研究中，我们发现 GGA 给药阻断了吗啡-CPP 的复燃。吗啡或 GGA 诱导核仁accumbens（NAc）和海马中 Trx-1、N-甲基-D-天冬氨酸受体 2B 亚基（NR2B）、磷酸化钙/钙调蛋白依赖性蛋白激酶 II（p-CaMKII）、磷酸化细胞外信号调节激酶（p-ERK）和磷酸化 cAMP 反应元件结合蛋白（p-CREB）的表达，而 GGA 处理的小鼠中，吗啡并未改变这些蛋白的表达。我们的结果表明，GGA 可能通过增强 Trx-1 的表达和调节 NR2B/ERK 通路来防止吗啡-CPP 的复燃。因此，我们认为 GGA 可能是治疗吗啡诱导复燃的有前途的候选药物。
