吗啡依赖条件性位置厌恶大鼠模型伏隔核壳区5-HT、5-HIAA浓度变化

发布时间：2018-06-20 12:12

本文选题：吗啡依赖 + 条件性位置厌恶　；参考：《新乡医学院》2013年硕士论文

【摘要】：背景药物依赖涉及到中枢神经系统功能广泛变化。研究提示5-HT系统与药物依赖有密切关系,5-HT能神经系统对脑内动机相关的奖赏环路调节可能是药物依赖中神经机制之一。目的测定慢性吗啡依赖大鼠条件性位置厌恶(CPA)模型建立前后、消退后及重建后伏隔核壳区细胞外液5-HT、5-HIAA7(?)平变化,初步探讨吗非依赖的神经生化机制。方法 1.69只SD大鼠随机分为研究组：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“催瘾注射”组(morphine+saline,MS)慢性生理盐水注射+纳洛酮催瘾组(saline+naloxone,SN)每组23只。 2.采用连续6.5天吗啡注射(10mg/kg,bid,IP)一次纳洛酮催瘾(0.3mg/kg,IP),同时与自制的条件性位置训练箱搭配建立CPA模型。 3.用微透析的方法分别在timel(微透析套管针植入术后3-5天),time2(Day59:00AM吗啡/生理盐水注射后30min),time3(Day5CPA行为训练后90min),time4(Day6纳洛酮注射后40min),time5(day7CPA测评后90min),time6(最后一次消退行为训练后90min),time7(Day14重建行为训练后90min)透出伏隔核壳区的细胞外液。 4.用高效液相色谱-电化学方法检测透析液中5-HT及其代谢产物5-HIAA浓度。结果 1.慢性吗啡注射与纳洛酮催瘾搭配(MN组)可成功建立CPA大鼠模型,表现出明显的仄恶动机,对伴药侧表现出明显的回避,CPA建立之后的大鼠经过连续7天的消退训练后CPA可以成功消退,消退后的CPA大鼠药物点燃时,可再次重建。 2.吗啡慢性注射后,MS组和MN组将大鼠伏隔核壳区的5-HT、5-HIAA水平高于对照组(P0.05)；注射纳洛酮后MN组5-HT、5-HIAA浓度明显降低(P0.01)；消退训练后,MN组5-HT、5-HIAA水平显著升高(P0.01)；药物点燃纳洛酮催瘾CPA重建后,MN组5-HT、5-HIAA水平显著降低(P0.01)。结论伏隔核壳区内5-HT参与吗啡依赖戒断所致CPA相关中枢厌恶动机,提示通过对5-HT的代谢和传递来改变中枢动机状态,可能是阿片依赖的临床治疗的潜在靶点之一。
[Abstract]:Background

The study suggests that the 5 - HT system is closely related to drug dependence , and the 5 - HT system may be one of the neural mechanisms in drug dependence .

Purpose

The changes of 5 - HT , 5 - HIAA7 ( ? ) levels in extracellular fluid of the isolated nuclear shell were measured before and after the establishment of chronic morphine dependent rat conditioned position aversion ( CPA ) model .

method

1.69 SD rats were randomly divided into two groups : morphine + naloxone ( MN ) and morphine + naloxone ( MN ) ; control group : morphine + saline ( MS ) + saline + naloxone ( SN ) group ( n = 23 ) .

2 . A continuous 6.5 - day morphine injection ( 10 mg / kg , bid , IP ) was used to treat naloxone ( 0.3mg / kg , IP ) , and the CPA model was established with the self - made conditioned place training box .

3 . The extracellular fluid of the isolated nuclear shell area was measured at timel ( 3 - 5 days after micro - dialysis trocar implantation ) , time2 ( Day59 : 00 AM morphine / physiological saline ) , time3 ( Day5 CPA behavior training 90 min ) , time5 ( 90 min after day 6 naloxone injection ) , time6 ( 90 min after the last regression behavior ) , time7 ( 90 min after the training of Day14 reconstruction ) .

4 . 5 - HT and its metabolite 5 - HIAA concentration were determined by HPLC - electrochemical method .

Results

1 . The rats model of CPA was successfully established by chronic morphine injection and naloxone ( MN group ) .

2 . After chronic morphine injection , the levels of 5 - HT and 5 - HIAA were higher in MS group and MN group than in the control group ( P0.05 ) .
The concentration of 5 - HT and 5 - HIAA in MN group decreased significantly after naloxone injection ( P0.01 ) .
The levels of 5 - HT and 5 - HIAA in MN group increased significantly ( P0.01 ) .
The 5 - HT and 5 - HIAA levels were significantly lower in MN group ( P0.01 ) .

Conclusion

5 - HT is involved in the central aversion to morphine dependence induced by morphine dependence . It suggests that the metabolism and transmission of 5 - HT may be one of the potential targets for clinical treatment of opioid dependence .
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.6

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