【摘要】：目的甲基苯丙胺(MA)成癮存在著性別差異，為了明確雌激素在MA成癮中的可能作用，本研究系統(tǒng)觀察了雌激素受體拮抗劑ICI182780（ICI）對雌性大鼠MA長短時程訓(xùn)練的獎賞以及覓藥行為的影響，同時分析了MA自身給藥后焦慮、抑郁行為和情感記憶的影響. 方法雌性Sprague-Dawley（SD）大鼠按固定比例1（FR1）程序進行MA(0.05mg·kg-1per infusion)靜脈自身給藥訓(xùn)練，訓(xùn)練12天，每天分別訓(xùn)練1小時或6小時。訓(xùn)練后，大鼠進行10天的行為消退，然后測定條件性線索和MA(1mg/kg)誘導(dǎo)的覓藥行為。最后對大鼠進行高架十字迷宮、強迫游泳和恐懼記憶的測試。結(jié)果長時程（6h）和短時程（1h）MA自身給藥訓(xùn)練后，平均有效鼻觸數(shù)有明顯差異，長時程MA攝入劑量明顯增加，，差異有顯著性差異（P0.01）。雌激素受體拮抗劑ICI慢性治療后對減低1h MA訓(xùn)練的大鼠有效鼻觸數(shù)有影響(P0.05)，對經(jīng)6h MA訓(xùn)練的大鼠有效鼻觸數(shù)則沒影響(P0.05)；但ICI處理后對長短時程訓(xùn)練的大鼠MA攝入總量均有減低作用，差異均有統(tǒng)計學(xué)意義（P0.01）。長時程訓(xùn)練的大鼠，消退第一天有效鼻觸數(shù)高于短時程訓(xùn)練大鼠（P0.01），ICI處理后對長時程和短時程訓(xùn)練雌性大鼠的消退行為沒有影響(P0.05)。在線索誘導(dǎo)的覓藥行為測試中，長時程訓(xùn)練的大鼠有效鼻觸數(shù)稍高于短時程訓(xùn)練的大鼠，但統(tǒng)計學(xué)沒有差異(P0.05)；ICI處理后對長時程和短時程訓(xùn)練雌性大鼠的覓藥行為沒有影響(P0.05)。在藥物引燃的MA重建測試中，長時程訓(xùn)練的大鼠有效鼻觸數(shù)稍高于短時程訓(xùn)練的大鼠，但統(tǒng)計學(xué)沒有差異(P0.05)，ICI處理的長時程和短時程訓(xùn)練大鼠有效鼻觸數(shù)與對照組沒有統(tǒng)計學(xué)差異(P0.05)。 在高架十字迷宮測試中，6h MA訓(xùn)練的雌性大鼠在閉臂滯留時間較1h MA訓(xùn)練的大鼠沒有差異，只有6h MA訓(xùn)練的ICI給藥組大鼠比對照組在閉臂滯留時間百分比升高(P0.05)。在強迫游泳測試中，與對照組相比，6h MA訓(xùn)練的雌性大鼠僵直不動的時間較0h MA訓(xùn)練的大鼠長(P0.01)； ICI給藥組相對于訓(xùn)練對照組有差異(P0.05)。 在24h條件性恐懼記憶測試中，與對照相比，6h MA訓(xùn)練的雌性大鼠僵直不動時間百分比縮短(P0.05)， ICI給藥組相對于訓(xùn)練對照組也明顯縮短(P0.01)。 在一周條件性恐懼記憶測試中，與對照組相比，短和長時程訓(xùn)練大鼠僵直不動時間百分比均明顯縮短(P0.01)， ICI給藥組相對于訓(xùn)練對照組也有明顯差異(P0.01)。 結(jié)論本研究發(fā)現(xiàn)隨著訓(xùn)練時間延長，大鼠攝入MA劑量增加，但覓藥行為沒有明顯差異；雌激素受體拮抗劑慢性處理可減少MA的攝入，提示內(nèi)源性雌激素功能與MA的攝入有密切關(guān)系。MA沒有明顯產(chǎn)生焦慮和抑郁樣行為，但可以明顯地損害認知功能。而ICI處理后可以減緩大鼠的焦慮情緒，易化抑郁情緒，并能減弱恐懼記憶的鞏固,本結(jié)果提示雌激素受體可能參與了MA的獎賞以及成癮后的認知功能障礙。
[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.
【學(xué)位授予單位】：寧波大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R749.7

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