CAJ | 학술논문

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(conditioned place aversion,CPA)建立前后,与成瘾密切相关的脑区伏隔核壳区(the shell of nucleus accumbens,AcbSH)内蛋白激酶A(protein kinase 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(10 mg/kg,BID,IP)后予1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,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.
목적 분석만성마배의뢰대서납락동최은계단조건성위치염악(conditioned place aversion,CPA)건립전후,여성은밀절상관적뇌구복격핵각구(the shell of nucleus accumbens,AcbSH)내단백격매A(protein kinase A,PKA)단백표체적괄응성변화,탐토아편의뢰계단후염악동궤형성적생물학기출.방법 1.장웅성Sprague-Dawley (SD)대서분위연구조(만성마배주사+납락동최은조morphine+ naloxone,MN),대조조(만성마배주사+생리염수“최은”조( morphine+ saline,MS),만성생리염수주사+납락동최은조( saline+ naloxone,SN),매조12지.채용만성마배주사(10 mg/kg,BID,IP)후여1차납락동(0.3 mg/kg)최은주사(동시여조건성위치훈련상탑배)건립대서CPA모형.2.재CPA건립전후,채용면역조직화학방법검측AcbSH내PKA단백표체정황.결과 CPA건립전,MN조PKA단백표체수평(109.33±5.508)여대조조MS조(111.86 ±8.688)화SN조(132.25 ±-4.844),차이무통계학의의(F=2.306,P=0.130).CPA건립후,각조PKA단백표체수평비교차이유통계학의의(F=36.516,P=0.000)기중MN조(109.50±4.661)고우MS조(126.50±3.697；P＜0.01),고우SN조(133.50 ±6.364；P＜0.01).결론 1.AcbSH내PKA단백적고표체도치적염악적중추상태,가능시CPA건립적관건적신경궤제.2.AcbSH내PKA적괄응성변화가능시물질의뢰계단후CPA상관신경가소성변화적중요분자기출.
Objective To explore neurobiological mechanisms of the withdrawal-induced aversion,the changes of protein kinase A(PKA) were measured in shell of accumbens nucleus (AcbSH) 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 immunohistochemistry in the AcbSH.Results Before the development of CPA,PKA expressions were no significant differences among the three groups in the AcbSH (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 AcbSH 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.