雌激素受体拮抗剂ICI182780对雌性大鼠甲基苯丙胺奖赏、重建和认知功能的影响
发布时间：2019-01-19 21:30
【摘要】：目的甲基苯丙胺(MA)成瘾存在着性别差异，为了明确雌激素在MA成瘾中的可能作用，本研究系统观察了雌激素受体拮抗剂ICI182780（ICI）对雌性大鼠MA长短时程训练的奖赏以及觅药行为的影响，同时分析了MA自身给药后焦虑、抑郁行为和情感记忆的影响. 方法雌性Sprague-Dawley（SD）大鼠按固定比例1（FR1）程序进行MA(0.05mg·kg-1per infusion)静脉自身给药训练，训练12天，每天分别训练1小时或6小时。训练后，大鼠进行10天的行为消退，然后测定条件性线索和MA(1mg/kg)诱导的觅药行为。最后对大鼠进行高架十字迷宫、强迫游泳和恐惧记忆的测试。结果长时程（6h）和短时程（1h）MA自身给药训练后，平均有效鼻触数有明显差异，长时程MA摄入剂量明显增加，，差异有显著性差异（P0.01）。雌激素受体拮抗剂ICI慢性治疗后对减低1h MA训练的大鼠有效鼻触数有影响(P0.05)，对经6h MA训练的大鼠有效鼻触数则没影响(P0.05)；但ICI处理后对长短时程训练的大鼠MA摄入总量均有减低作用，差异均有统计学意义（P0.01）。长时程训练的大鼠，消退第一天有效鼻触数高于短时程训练大鼠（P0.01），ICI处理后对长时程和短时程训练雌性大鼠的消退行为没有影响(P0.05)。在线索诱导的觅药行为测试中，长时程训练的大鼠有效鼻触数稍高于短时程训练的大鼠，但统计学没有差异(P0.05)；ICI处理后对长时程和短时程训练雌性大鼠的觅药行为没有影响(P0.05)。在药物引燃的MA重建测试中，长时程训练的大鼠有效鼻触数稍高于短时程训练的大鼠，但统计学没有差异(P0.05)，ICI处理的长时程和短时程训练大鼠有效鼻触数与对照组没有统计学差异(P0.05)。 在高架十字迷宫测试中，6h MA训练的雌性大鼠在闭臂滞留时间较1h MA训练的大鼠没有差异，只有6h MA训练的ICI给药组大鼠比对照组在闭臂滞留时间百分比升高(P0.05)。在强迫游泳测试中，与对照组相比，6h MA训练的雌性大鼠僵直不动的时间较0h MA训练的大鼠长(P0.01)； ICI给药组相对于训练对照组有差异(P0.05)。 在24h条件性恐惧记忆测试中，与对照相比，6h MA训练的雌性大鼠僵直不动时间百分比缩短(P0.05)， ICI给药组相对于训练对照组也明显缩短(P0.01)。 在一周条件性恐惧记忆测试中，与对照组相比，短和长时程训练大鼠僵直不动时间百分比均明显缩短(P0.01)， ICI给药组相对于训练对照组也有明显差异(P0.01)。 结论本研究发现随着训练时间延长，大鼠摄入MA剂量增加，但觅药行为没有明显差异；雌激素受体拮抗剂慢性处理可减少MA的摄入，提示内源性雌激素功能与MA的摄入有密切关系。MA没有明显产生焦虑和抑郁样行为，但可以明显地损害认知功能。而ICI处理后可以减缓大鼠的焦虑情绪，易化抑郁情绪，并能减弱恐惧记忆的巩固,本结果提示雌激素受体可能参与了MA的奖赏以及成瘾后的认知功能障碍。
[Abstract]:Objective to investigate the possible role of estrogen in MA addiction, there is a gender difference in methamphetamine (MA) addiction. In this study, the effects of estrogen receptor antagonist (ICI182780 (ICI) on the reward and drug seeking behavior of MA in female rats were systematically observed, and the effects of MA on anxiety, depression and emotional memory after administration of MA were analyzed. Methods female Sprague-Dawley (SD) rats were treated with MA (0.05mg kg-1per infusion) intravenously for 12 days for 1 hour or 6 hours per day according to a fixed ratio 1 (FR1) program. After training, the behavior of rats subsided for 10 days, then conditioned cues and MA (1mg/kg) induced drug seeking behavior were measured. Finally, the rats were tested by elevated cross maze, forced swimming and fear memory. Results after self-administration of MA for long time (6 h) and short time (1 h), the average effective nasal contact number was significantly different, and the intake dose of long term MA was significantly increased (P0.01). After chronic treatment with estrogen receptor antagonist (ICI), there was an effect on the number of effective nasal contacts of rats after 1 h MA training (P0.05), but no effect on the number of effective nasal contacts of rats trained for 6 h MA (P0.05). However, the total MA intake of rats treated with ICI was significantly lower than that of control group (P0.01). The number of effective nasal contacts on the first day after long term training was higher than that of short term training rats (P0. 01), ICI treatment had no effect on the regression behavior of long term and short duration training female rats (P0.05). In the cue-induced drug seeking behavior test, the number of effective nasal contacts of long-term training rats was slightly higher than that of short-term training rats, but there was no statistical difference (P0.05). ICI treatment had no effect on the drug seeking behavior of long term and short term training female rats (P 0.05). In the MA reconstruction test of drug ignition, the number of effective nasal contacts in long-term training rats was slightly higher than that in short-term training rats, but there was no statistical difference (P0.05). There was no significant difference in the number of effective nasal contacts between the ICI treatment group and the control group (P0.05). In the elevated cross maze test, the retention time of female rats trained at 6 h MA was not different from that of rats trained for 1 h MA, only the percentage of retention time in closed arm was increased in the 6 h MA training group compared with that in the control group (P0.05). In the forced swimming test, compared with the control group, the female rats trained for 6 h MA had longer time of rigidity than the rats trained for 0 h MA (P0.01); ICI compared with the control group (P0.05). In the 24h conditioned fear memory test, compared with the control group, the percentage of stiffness time of 6h MA training female rats was shorter than that of the control group (P0.05) compared with the training control group (P0.01). In one week conditioned fear memory test, compared with the control group, the percentage of stiffness time in the short and long term training group was significantly shorter than that in the control group (P0.01), ICI group was also significantly different from the training control group (P0.01). Conclusion with the prolongation of training time, the dose of MA increased in rats, but there was no significant difference in drug seeking behavior. Chronic treatment with estrogen receptor antagonist can reduce the intake of MA, suggesting that endogenous estrogen function is closely related to the intake of MA. MA has no significant anxiety and depressive behavior, but can significantly damage cognitive function. The results suggested that estrogen receptor may be involved in the reward of MA and the cognitive dysfunction after addiction.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.7
本文编号：2411776
[Abstract]:Objective to investigate the possible role of estrogen in MA addiction, there is a gender difference in methamphetamine (MA) addiction. In this study, the effects of estrogen receptor antagonist (ICI182780 (ICI) on the reward and drug seeking behavior of MA in female rats were systematically observed, and the effects of MA on anxiety, depression and emotional memory after administration of MA were analyzed. Methods female Sprague-Dawley (SD) rats were treated with MA (0.05mg kg-1per infusion) intravenously for 12 days for 1 hour or 6 hours per day according to a fixed ratio 1 (FR1) program. After training, the behavior of rats subsided for 10 days, then conditioned cues and MA (1mg/kg) induced drug seeking behavior were measured. Finally, the rats were tested by elevated cross maze, forced swimming and fear memory. Results after self-administration of MA for long time (6 h) and short time (1 h), the average effective nasal contact number was significantly different, and the intake dose of long term MA was significantly increased (P0.01). After chronic treatment with estrogen receptor antagonist (ICI), there was an effect on the number of effective nasal contacts of rats after 1 h MA training (P0.05), but no effect on the number of effective nasal contacts of rats trained for 6 h MA (P0.05). However, the total MA intake of rats treated with ICI was significantly lower than that of control group (P0.01). The number of effective nasal contacts on the first day after long term training was higher than that of short term training rats (P0. 01), ICI treatment had no effect on the regression behavior of long term and short duration training female rats (P0.05). In the cue-induced drug seeking behavior test, the number of effective nasal contacts of long-term training rats was slightly higher than that of short-term training rats, but there was no statistical difference (P0.05). ICI treatment had no effect on the drug seeking behavior of long term and short term training female rats (P 0.05). In the MA reconstruction test of drug ignition, the number of effective nasal contacts in long-term training rats was slightly higher than that in short-term training rats, but there was no statistical difference (P0.05). There was no significant difference in the number of effective nasal contacts between the ICI treatment group and the control group (P0.05). In the elevated cross maze test, the retention time of female rats trained at 6 h MA was not different from that of rats trained for 1 h MA, only the percentage of retention time in closed arm was increased in the 6 h MA training group compared with that in the control group (P0.05). In the forced swimming test, compared with the control group, the female rats trained for 6 h MA had longer time of rigidity than the rats trained for 0 h MA (P0.01); ICI compared with the control group (P0.05). In the 24h conditioned fear memory test, compared with the control group, the percentage of stiffness time of 6h MA training female rats was shorter than that of the control group (P0.05) compared with the training control group (P0.01). In one week conditioned fear memory test, compared with the control group, the percentage of stiffness time in the short and long term training group was significantly shorter than that in the control group (P0.01), ICI group was also significantly different from the training control group (P0.01). Conclusion with the prolongation of training time, the dose of MA increased in rats, but there was no significant difference in drug seeking behavior. Chronic treatment with estrogen receptor antagonist can reduce the intake of MA, suggesting that endogenous estrogen function is closely related to the intake of MA. MA has no significant anxiety and depressive behavior, but can significantly damage cognitive function. The results suggested that estrogen receptor may be involved in the reward of MA and the cognitive dysfunction after addiction.
【学位授予单位】：宁波大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.7
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