Inhibition of Geranylgeranylacetone on cholecystokinin-B receptor, BDNF and dopamine D1 receptor induced by morphine
Inhibition of Geranylgeranylacetone on cholecystokinin-B receptor, BDNF and dopamine D1 receptor induced by morphine
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DOI：
10.1016/j.bbrc.2021.12.034
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发表时间：
2021-12-20
影响因子：
3.1
通讯作者：
Bai, Jie
中科院分区：
文献类型：
--
作者：
Guo, Ningning;Zhang, Le;Bai, Jie
吗啡是一种止痛和滥用药物。吗啡通过激活由腹侧被盖区（VTA）和中脑核（NAc）组成的多巴胺能奖赏系统而产生成瘾。胆囊收缩素（Cholecystokinin，CCK）是一种肠-脑神经肽，参与吗啡依赖。脑源性神经营养因子（BDNF）是一种神经营养因子，在调节成瘾中起作用。香叶基香叶基丙酮（GGA）是一种保护胃粘膜损伤和保护神经元的药物。我们前期的研究表明，GGA通过诱导硫氧还蛋白1（Trx 1）的表达阻断吗啡诱导的戒断和复吸。本研究旨在探讨胆囊收缩素B受体（CCKB receptor）和脑源性神经营养因子（BDNF）是否与GGA抑制吗啡成瘾有关。本研究首先建立了条件性位置偏爱（CPP）模型，再次证实了GGA对吗啡CPP表达的抑制作用。结果表明，吗啡可增加小鼠腹侧被盖区和腹侧被盖区多巴胺D1受体、酪氨酸羟化酶（TH）、CCKB受体和BDNF的表达，而GGA可抑制吗啡的这种作用。这些结果表明，多巴胺能系统中的CCK和BDNF与GGA阻断吗啡CPP的作用有关。(C)2021年，任作家。爱思唯尔公司出版
Morphine is the pain releasing and abusing drug. Morphine leads to addiction by activating dopaminergic rewarding system consisted of the ventral tegmental area (VTA) and nucleus accumbens (NAc). Cholecystokinin (CCK) is a gut-brain neuropeptide and involved in morphine dependence. Brain-derived neurotrophic factor (BDNF) is a neurotrophin and plays roles in regulating addiction. Geranylgeranylacetone (GGA) is a medicine of protecting gastric mucosal injury and protecting neurons. Our previous study showed that GGA blocked morphine-induced withdrawal and relapse through inducing thioredoxin 1(Trx1). In this study, we investigated that whether cholecystokinin-B receptor (CCKB receptor) and BDNF were related to GGA inhibition on morphine addiction. At first, we made conditioned place preference (CPP) model and confirmed again that GGA blocked the expression of morphine-CPP in present study. Then, our results showed that morphine increased the expressions of dopamine D1 receptor, tyrosine hydroxylase (TH), CCKB receptor and BDNF in the VTA and NAc in mice, which was inhibited by GGA. These results suggest that CCK and BDNF in dopaminergic systems are associated with the role of GGA blocking morphine-CPP. (C) 2021 The Authors. Published by Elsevier Inc.