慢性吗啡依赖大鼠条件性位置厌恶模型杏仁中央核蛋白激酶A表达变化

目的:分析慢性吗啡依赖大鼠纳洛酮催瘾戒断条件性位置厌恶(CPA)建立前后、消退后及重建后,与成瘾密切相关的脑区杏仁中央核(CeA)内蛋白激酶A(PKA)蛋白表达的适应性变化,探讨阿片依赖戒断后厌恶动机形成的生物学基础。方法:①将雄性SD大鼠分为实验组(慢性吗啡注射+纳洛酮催瘾组,MN),对照组(慢性吗啡注射+生理盐水催瘾组,MS),慢性生理盐水注射+纳洛酮催瘾组,SN),每组24只。采用慢性吗啡注射(10 mg/kg,BID,ip)后给予一次纳洛酮(0.3 mg/kg)催瘾注射(同时与条件性位置训练箱搭配)建立大鼠CPA模型。②在CPA建立前后、消退后及重建后,采用免疫组织化学方法检测CeA内PKA蛋白表达情况。结果:MN组在CPA建立前后、消退后及重建后CeA内PKA的蛋白表达出现适应性变化(P<0.05),建立后(Day7,134.43±4.481,P<0.05),消退后(Day13,141.01±3.360,P<0.01)及重建后(Day14,137.18±40.330,P<0.05)PKA蛋白表达水平均低于建立前(Day5,124.48±6.722)。而MS组(P>0.05)和SN组(P>0.05)在CPA的各个时间点PKA的蛋白表达变化差异均无显著性。结论:①CeA内PKA蛋白的低表达导致的厌恶的中枢状态,可能是CPA建立的关键的神经机制。②CeA内PKA的适应性变化可能是物质依赖戒断后CPA相关神经可塑性变化的重要分子基础。

Changes of protein kinase A expressions in central amygdaloid nuclei during the process of chronic morphine-induced conditioned place aversion in rats

Objective: To explore neurobiological mechanisms of the withdrawal-induced aversion.The changes of protein kinase A were measured in central amygdaloid nucleis(CeA) of conditioned place aversion(CPA) model rats.Methods: ① All 72 male SD rats were divided into three groups,model group(MN group),and control group(MS group and SN group).MN group was injected with morphine,6.5 days,10 mg/kg,intraperitoneally(ip),twice per day,naloxone injection,0.3 mg/kg,ip,along with conditioned place aversion training,to develop the CPA model.The MS group was administrated equivalent volume of morphine and saline.Also the SN group was injected with equivalent volume of saline and naloxone.②During the process of morphine-induced CPA,the expression of protein kinase A was assayed with immunohistochemistry in the CeA.Results: In the MN group,protein kinase A expressions in the CeA occurred adaptive changes at different points of CPA(P<0.05).Protein kinase A expressions after establishment(Day7,134.43±4.481,P<0.05),and after extinction(Day13,141.01±3.360,P<0.01),and after reinstatement(Day14,137.18±40.330,P<0.05)were also lower than those before the establishment of the CPA(Day5,124.48±6.722).However,PKA expressions were not significantly different both in MS group(P>0.05)and SN group(P>0.05).Conclusion: ①Protein kinase A expression,in turn regulating the aversion expression,in the CeA probably is a key pathway contributing to the development of CPA.②The neuroadaptation mediated by protein kinase A may be one of the important molecular underpinnings of CPA.