多巴胺D3受体在吗啡依赖大鼠条件性位置偏爱及戒断反应中的作用  

Role of Dopamine D3 Receptor in Conditioned Place Preference and Withdrawal Response in Morphine-Dependent Rats

作　　者：赖佳灵 张耀中 杜桂芝[2] 王昕[3] 刘巧凤[1] Lai Jialing;Zhang Yaozhong;Du Guizhi;Wang Xin;Liu Qiaofeng(Department of Pathology and Pathophysiology,Chengdu Medical College,Chengdu 610500,China;Department of Anesthesiology,West China Hospital of Sichuan University,Chengdu 610041,China;Department of Pathogenic Biology,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院病理学与病理生理学教研室,成都610500 [2]四川大学华西医院麻醉科,成都610041 [3]成都医学院病原生物学教研室,成都610500

出　　处：《成都医学院学报》2025年第2期181-185,共5页Journal of Chengdu Medical College

基　　金：国家自然科学基金项目(No:8247131421);四川省成都医学院应用心理学研究中心项目(No:CSXL-24207)。

摘　　要：目的研究多巴胺受体(D3R)在吗啡依赖大鼠条件性位置偏爱反应及戒断反应中的作用。方法60只6~8周龄Wistar雄性健康大鼠体重180~220 g,随机分为6组,Ⅰ组(生理盐水组)、Ⅱ组(吗啡组)、Ⅲ组(D3R激动剂ML417+吗啡组)、Ⅳ组(D3R拮抗剂GSK598809+吗啡组)、Ⅴ组(ML417+盐水组)、Ⅵ组(GSK598809+盐水组)。Ⅰ组大鼠腹腔注射生理盐水后放入黑色非伴药箱30 min,Ⅱ组腹腔注射吗啡后放入白色伴药箱30 min,次日记录大鼠在黑白箱中的停留时间。通过计算大鼠在白箱中的停留时间与预试期的差值,评估条件性偏爱的形成,当观察到统计学差异时,说明大鼠对白箱表现出明显的偏好。结果与Ⅰ组比较,Ⅱ组大鼠在白箱的停留时间增加(P<0.05)。与Ⅱ组比较,Ⅲ组大鼠在白箱的停留时间进一步增加(P<0.01),同时Raf和磷酸化ERK(p-ERK)的表达也增强(P<0.05)。相反,与Ⅱ组比较,Ⅳ组大鼠在白箱的停留时间减少(P<0.001),Raf和p-ERK的水平也明显降低(P<0.05或P<0.01),戒断分数降低(P<0.001)。结论D3受体在维持吗啡诱导的条件性位置偏爱反应和戒断反应方面发挥作用,D3R可能通过下调中脑导水管灰质区中的Raf-ERK信号通路,从而减轻对吗啡的偏好。Objective The study investigates the role of dopamine D3 receptor(D3R)in conditioned place preference(CPP)and withdrawal responses in morphine-dependent rats.Methods Sixty healthy male Wistar rats aged 6-8 weeks,weighing 180-220 g,were randomly divided into six groups:GroupⅠ(normal saline group),GroupⅡ(morphine group),GroupⅢ(D3 receptor agonist ML417+morphine group),GroupⅣ(D3 receptor antagonist GSK598809+morphine group),GroupⅤ(ML417+saline group),and GroupⅥ(GSK598809+saline group).Rats in GroupⅠreceived intraperitoneal injection of normal saline and were then placed in a black non-drug-associated box for 30 min.Rats in GroupⅡwere administered morphine via intraperitoneal injection and then placed in a white drug-associated box for 30 min.Their residence time in the black and white boxes were recorded the following day.The formation of CPP was assessed by calculating the difference between the time the rat spent in the white box and the time it spent in the black box during the pre-trial period.Statistical differences indicated a clear preference of the rats for the white box.Results Compared to GroupⅠ,rats in GroupⅡspent significantly more time in the white chamber(P<0.05).Compared to GroupⅡ,rats in GroupⅢhad a further increase in the time spent in the white chamber(P<0.01),and exhibited enhanced expression of Raf and phosphorylated extracellular signal-regulated kinase(p-ERK)(P<0.05).In contrast,compared to GroupⅡ,rats in GroupⅣspent significantly less time in the white chamber(P<0.001),and showed a marked reduction in Raf and p-ERK levels(P<0.05 or P<0.01)and a significant decrease in withdrawal scores(P<0.001).Conclusion D3R plays a crucial role in maintaining morphine-induced CPP and withdrawal responses.D3R may alleviate morphine preference by down-regulating the Raf-ERK signaling pathway in the midbrain periaqueductal gray(PAG).

关 键 词：吗啡 多巴胺D3受体 RAF 细胞外信号调节激酶 条件性位置偏爱反应 中脑导水管灰质区 

分 类 号：R614[医药卫生—麻醉学]