慢性吗啡依赖大鼠条件性位置厌恶模型伏隔核壳区蛋白激酶A表达变化  

Changes of protein kinase A expressions in shell of accumbens nucleus during the process of chronic morphine-induced conditioned place aversion in rats

作　　者：宋秀花[1] 李文强[1] 张景丹[1] 石玉中[1] 张瑞岭[1] 李毅 

机构地区：[1]新乡医学院第二附属医院,河南省生物精神病学重点实验室,新乡453002 [2]武汉市精神卫生中心

出　　处：《中华行为医学与脑科学杂志》2012年第3期232-234,共3页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金

摘　　要：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（conditionedplaceaversion，CPA）建立前后，与成瘾密切相关的脑区伏隔核壳区（theshellofnucleusaccumbens，AcbSH）内蛋白激酶A（proteinkinaseA，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Sprague-Dawley（SD）大鼠分为研究组（慢性吗啡注射＋纳洛酮催瘾组morphine＋naloxone，MN），对照组（慢性吗啡注射＋生理盐水“催瘾”组（morphine＋saline，MS），慢性生理盐水注射＋纳洛酮催瘾组（saline＋naloxone，SN），每组12只。采用慢性吗啡注射（10mg／kg，BID，IP）后予1次纳洛酮（0．3mg／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，采用免疫组织化学方法检测AcbSH内PKA蛋白表达情况。结果CPA建立前，MN组PKA蛋白表达水平（109．33±5．508）与对照组MS组（111．86±8．688）和SN组（132．25±4．844），差异无统计学意义F=2．306，P=0．130）。CPA建立后，各组PKA蛋白表达水平比较差异有统计学意义（F=36．516，P=0．000）其中MN组（109．50±4．661）高于MS组（126．50±3．697；P〈0．01），高于SN组（133．50±6．364；P〈0．01）。结论1．AcbSH内PKA蛋白的高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。2．AcbSH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。Objective To explore neurobiological mechanisms of the withdrawal-induced aversion, the changes of protein kinase A（PKA） were measured in shell of aecumbens nucleus （AebSH） of CPA model rats. Methods 1. All 36 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, 10mg/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. 2. During the development of CPA, the expression of protein kinase A was assayed with immunohistoehemistry in the AcbSH. Results Before the development of CPA, PKA expres- sions were no significant differences among the three groups in the AebSH （F= 2. 306, P= 0. 130）. However,after development of CPA , PKA expressions showed significant differences among the three groups（F = 36. 516, P = 0.000）. The average gray intensity of MN group （109.50 ± 4. 661 ） was apparently higher than the MS group （126.50±3.697, P〈0.01） ,than the SN group （133.50 ±6.364, P〈0.01）. Conclusions 1. Protein kinase A expression,leading to the aversion in the AebSH probably is a key pathway contributing to the development of CPA. 2. The neuroadaptation mediated by PKA may be one of important molecular underpinnings of CPA.

关 键 词：条件性位置厌恶 蛋白激酶A 免疫组化 

分 类 号：R96[医药卫生—药理学]