内侧隔核胆碱能神经在海洛因成瘾和复吸中的作用
发布时间：2018-08-11 16:58
【摘要】：目的 观察选择性损伤内侧隔核胆碱能神经对大鼠海洛因自身给药获得、消退、复吸及空间学习记忆的影响；并观察损伤内侧隔核投射至海马腹侧下托胆碱能神经对海洛因成瘾大鼠复吸及空间学习记忆的影响。 方法 实验一：雄性SD大鼠随机分为损伤组（n=8）和对照组(n=7)，损伤组注射192IgG-Saporin（0.25μg）至内侧隔核（AP+0.4, ML0, DV－5.5），对照组注射等量无菌生理盐水；注射后恢复一周，动物进行FR1海洛因自身给药获得测试(4h)，之后进行消退(2h)和线索诱导的海洛因觅药行为测试(2h)；消退2～4天后进行海洛因诱导的觅药行为恢复测试(2h)，测试前10min腹腔注射海洛因（0.25mg/kg）；之后用Morris水迷宫测试空间定位航行能力和空间探索能力观察两组大鼠空间学习记忆能力，并与未成瘾组大鼠（n=8）进行比较；免疫组化ABC法染色Chat阳性细胞，观察内侧隔核胆碱能神经元损伤程度。 实验二：雄性SD大鼠构建海洛因自身给药模型，戒断2周；戒断期中枢埋管至海马腹侧下托（AP+0.4, ML0, DV－5.5），随机分为损伤组（n=7）和对照组（n=6），损伤组双侧注射192IgG-Saporin（每侧0.25μg），对照组注射等量无菌盐水；一周后进行海洛因觅药行为测试，消退2～4天后进行海洛因诱导的觅药行为测试，测试前10min腹腔注射海洛因（0.25mg/kg）；之后两组动物进行Morris水迷宫测试，，测试后动物用免疫组化观察胆碱能神经的损伤程度。 结果 实验一：内侧隔核胆碱能神经损伤后在海洛因自身给药训练的获得测试中的有效鼻触数较对照组没有显著性差异，海洛因给药次数在前期没有差异，随着训练时间延长，损伤组给药次数显著高于对照组（P＜0.05）；在消退训练和线索诱导的海洛因觅药行为测试中两组的触鼻数没有显著性差异；而海洛因诱导的觅药行为测试中，损伤组有效触鼻数（2h）较对照组显著升高（P＜0.05）；Morris水迷宫测试中损伤组和对照组潜伏期、总运动路程和穿越平台次数没有显著性差异，但两组在定位航行试验和空间探索试验中表现均差于未成瘾组大鼠（P＜0.05）。 实验二：海马腹侧下托损伤组和对照组在线索诱导的海洛因觅药行为测试和海洛因诱导的觅药行为测试中的有效鼻触数没有显著性差异；Morris水迷宫测试中两组潜伏期、总运动路程、平均速度和穿越平台次数也没有显著性差异。 结论 内侧隔核胆碱能神经损伤可增加海洛因自身给药行为，促进海洛因诱导的觅药行为恢复，可见内侧胆碱能神经损伤改变了海洛因的奖赏效应，促进了对海洛因的渴求，提示胆碱能神经可能对药物奖赏和复吸有一定的调节作用。内侧隔核胆碱能神经损伤大鼠在海洛因诱导的觅药行为测试中表现出后期觅药行为增强，提示或因抑制控制能力减弱。海洛因成瘾损害了正常的空间学习记忆功能，或是内侧隔核胆碱能神经大鼠海洛因成瘾后的空间学习记忆与对照组没有显著性差异的原因。内侧隔核投射至腹侧下托的胆碱能损伤对海洛因复吸行为没有影响，提示内侧隔核投射至腹侧下托的胆碱能神经投射可能不参与海洛因复吸过程。
[Abstract]:objective
The effects of selective injury of the cholinergic nerve in the medial septal nucleus on the acquisition, regression, relapse and spatial learning and memory of heroin-addicted rats were observed.
Method
Experiment 1: Male SD rats were randomly divided into injury group (n=8) and control group (n=7). Injury group was injected 192IgG-Saporin (0.25 ug) to medial septal nucleus (AP+0.4, ML0, DV-5.5), and control group was injected with the same amount of sterile saline. After one week of recovery, the animals were tested for FR1 heroin self-administration (4h), and then subsided (2h) and cue inducement. Heroin-induced drug-seeking behavior recovery test (2h) was performed 2-4 days after withdrawal. Heroin (0.25mg/kg) was injected intraperitoneally 10 minutes before withdrawal. Morris water maze was used to test spatial navigation ability and spatial exploration ability to observe the spatial learning and memory ability of rats in both groups, and compared with the non-addicted group. The Chat positive cells were stained by ABC immunohistochemistry to observe the degree of injury of cholinergic neurons in the medial septal nucleus.
Experiment 2: Male SD rats were randomly divided into injury group (n = 7) and control group (n = 6), bilateral injection of 192 IgG-Saporin (0.25 UG on each side) and control group (0.25 UG on each side) with the same amount of sterile saline, and heroin foraging was performed one week later. Heroin-induced drug-seeking behavior was tested 2-4 days after withdrawal, and heroin (0.25 mg/kg) was injected intraperitoneally 10 minutes before withdrawal. Morris water maze test was performed in both groups. The degree of cholinergic nerve injury was observed by immunohistochemistry.
Result
Experiment 1: There was no significant difference in the number of effective nasal contacts in the test of heroin self-administered training after medial septal nucleus cholinergic nerve injury compared with the control group. There was no difference in the number of heroin administered in the earlier period. With the extension of training time, the number of drug administered in the injury group was significantly higher than that in the control group (P < 0.05). There was no significant difference in the number of contact noses between the two groups in heroin seeking behavior test, but the number of effective contact noses (2h) in the injury group was significantly higher than that in the control group (P However, the performance of the two groups was worse than that of the non-addicted group (P<0.05).
Experiment 2: There was no significant difference in the number of effective nasal contacts between the ventral hypothalamus injury group and the control group in the wire-induced heroin-seeking behavior test and heroin-induced drug-seeking behavior test.
conclusion
Injury of the cholinergic nerve in the medial septal nucleus can increase heroin self-administering behavior and promote heroin-induced drug-seeking behavior recovery. It can be seen that the medial cholinergic nerve injury alters heroin reward effect and promotes heroin craving, suggesting that the cholinergic nerve may regulate drug reward and relapse. Heroin addiction impaired normal spatial learning and memory function, or the spatial learning and memory of rats with medial septal nucleus cholinergic nerve after heroin addiction were not significantly different from the control group. The cholinergic damage projected from the medial septal nucleus to the ventral inferior fossa did not affect heroin relapse behavior, suggesting that the cholinergic nerve projection from the medial septal nucleus to the ventral inferior fossa may not be involved in heroin relapse.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.64
本文编号：2177643
[Abstract]:objective
The effects of selective injury of the cholinergic nerve in the medial septal nucleus on the acquisition, regression, relapse and spatial learning and memory of heroin-addicted rats were observed.
Method
Experiment 1: Male SD rats were randomly divided into injury group (n=8) and control group (n=7). Injury group was injected 192IgG-Saporin (0.25 ug) to medial septal nucleus (AP+0.4, ML0, DV-5.5), and control group was injected with the same amount of sterile saline. After one week of recovery, the animals were tested for FR1 heroin self-administration (4h), and then subsided (2h) and cue inducement. Heroin-induced drug-seeking behavior recovery test (2h) was performed 2-4 days after withdrawal. Heroin (0.25mg/kg) was injected intraperitoneally 10 minutes before withdrawal. Morris water maze was used to test spatial navigation ability and spatial exploration ability to observe the spatial learning and memory ability of rats in both groups, and compared with the non-addicted group. The Chat positive cells were stained by ABC immunohistochemistry to observe the degree of injury of cholinergic neurons in the medial septal nucleus.
Experiment 2: Male SD rats were randomly divided into injury group (n = 7) and control group (n = 6), bilateral injection of 192 IgG-Saporin (0.25 UG on each side) and control group (0.25 UG on each side) with the same amount of sterile saline, and heroin foraging was performed one week later. Heroin-induced drug-seeking behavior was tested 2-4 days after withdrawal, and heroin (0.25 mg/kg) was injected intraperitoneally 10 minutes before withdrawal. Morris water maze test was performed in both groups. The degree of cholinergic nerve injury was observed by immunohistochemistry.
Result
Experiment 1: There was no significant difference in the number of effective nasal contacts in the test of heroin self-administered training after medial septal nucleus cholinergic nerve injury compared with the control group. There was no difference in the number of heroin administered in the earlier period. With the extension of training time, the number of drug administered in the injury group was significantly higher than that in the control group (P < 0.05). There was no significant difference in the number of contact noses between the two groups in heroin seeking behavior test, but the number of effective contact noses (2h) in the injury group was significantly higher than that in the control group (P However, the performance of the two groups was worse than that of the non-addicted group (P<0.05).
Experiment 2: There was no significant difference in the number of effective nasal contacts between the ventral hypothalamus injury group and the control group in the wire-induced heroin-seeking behavior test and heroin-induced drug-seeking behavior test.
conclusion
Injury of the cholinergic nerve in the medial septal nucleus can increase heroin self-administering behavior and promote heroin-induced drug-seeking behavior recovery. It can be seen that the medial cholinergic nerve injury alters heroin reward effect and promotes heroin craving, suggesting that the cholinergic nerve may regulate drug reward and relapse. Heroin addiction impaired normal spatial learning and memory function, or the spatial learning and memory of rats with medial septal nucleus cholinergic nerve after heroin addiction were not significantly different from the control group. The cholinergic damage projected from the medial septal nucleus to the ventral inferior fossa did not affect heroin relapse behavior, suggesting that the cholinergic nerve projection from the medial septal nucleus to the ventral inferior fossa may not be involved in heroin relapse.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.64
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本文编号：2177643
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