氧化震颤素及其与SCH 23390联合给药对大鼠冲动决策的影响

发布时间：2018-11-07 07:38

【摘要】：冲动行为是指因考虑不周、反应过快、风险过度或不合时宜从而导致不良后果的一类行为。冲动决策属于冲动行为中的一种。它是指个体在做出决策时,倾向于选择即时小额奖赏而非延迟大额奖赏,或者倾向于选择高风险大额奖赏而非低风险小额奖赏的行为。已有研究表明,胆碱能系统、多巴胺能系统在冲动决策行为中发挥了重要的作用。同时,当个体的先天冲动水平不同时,它们起作用的方式可能不同。目前,已有不少研究考察了多巴胺影响冲动决策的神经生物学机制。但有关胆碱能神经递质影响个体冲动决策的方式仍有待进一步研究。在内侧前额皮层等与冲动决策相关的脑区内,胆碱能系统和多巴胺能系统存在着交互作用。因此,本研究考察先天冲动水平不同时,毒蕈碱型胆碱类药物是否可以间接作用于多巴胺能系统从而影响个体的冲动决策水平。实验选用16只Sprague-Dawley大鼠进行延迟折扣任务训练。整个实验程序包括训练期和测试期两个阶段。实验一的目的是建立高、低冲动大鼠的延迟折扣模型。实验二考察了毒蕈碱型受体激动剂氧化震颤素(0.025mg/kg,0.05mg/kg,0.075mg/kg)对高、低冲动大鼠冲动决策的影响。实验三考察氧化震颤素(0.05mg/kg)和D1样受体拮抗剂SCH23390(0.005mg/kg,0.0075mg/kg,0.01mg/kg)联合给药对高、低冲动大鼠冲动决策的影响。实验结果发现：在实验一中,将大鼠分为高冲动组和低冲动组(每组8只)。这两组大鼠的大额奖赏选择比例存在显著性差异。在实验二中,0.05mg/kg、0.075mg/kg氧化震颤素能够显著提高高冲动大鼠的大额奖赏选择比例,降低低冲动大鼠的大额奖赏选择比例。但0.075mg/kg氧化震颤素显著提高了两组大鼠的反应时和漏报比例。在实验三中,0.005mg/kg、0.0075mg/kg、0.01mg/kg SCH23390显著抑制了0.05mg/kg氧化震颤素所诱发的高冲动大鼠大额奖赏选择比例升高的结果,0.0075mg/kg SCH23390显著增强了0.05mg/kg氧化震颤素所诱发的低冲动大鼠大额奖赏选择比例降低的结果。但0.05mg/kg氧化震颤素和0.01mg/kg SCH23390联合给药使两组大鼠选择大额奖赏(延迟0s投递时)的比例显著降低,使两组大鼠的反应时、高冲动组大鼠的漏报比例显著升高。研究结果表明,氧化震颤素能够降低高冲动大鼠的冲动决策水平,提高低冲动大鼠的冲动决策水平。SCH23390能够抑制氧化震颤素所诱发的高冲动大鼠冲动决策水平降低的现象,增强氧化震颤素所诱发的低冲动大鼠冲动决策水平升高的现象。这一结果初步表明毒蕈碱型胆碱类药物可以间接作用于多巴胺能系统从而影响个体的冲动决策水平。
[Abstract]:Impulsive behavior is a kind of behavior which is due to improper consideration, overreaction, excessive risk or untimely, which leads to adverse consequences. Impulse decision is a kind of impulsive behavior. It refers to the behavior that individuals tend to choose immediate small reward rather than delay large reward, or high risk large reward rather than low risk small reward when making decision. It has been shown that cholinergic system and dopaminergic system play an important role in impulsive decision-making. At the same time, when individuals have different levels of innate impulses, they may act in different ways. At present, many studies have investigated the neurobiological mechanism of dopamine affecting impulsive decision-making. However, the influence of cholinergic neurotransmitters on individual impulse decision-making needs further study. There is interaction between cholinergic system and dopaminergic system in the medial prefrontal cortex and other brain regions related to impulse decision. Therefore, we investigated whether muscarinic choline can indirectly affect dopaminergic system and affect individual impulse decision level. Sixteen Sprague-Dawley rats were trained with delayed discount task. The whole experiment procedure includes two stages: training period and test period. The purpose of experiment one is to establish the model of delay discount in rats with high and low impulse. In experiment 2, the effects of oxytremor (0.025 mg / kg), a muscarinic receptor agonist (0.025 mg / kg), on impulsive decision-making in rats with high and low impulses were investigated. The effects of 0.05mg/kg and SCH23390 (0.005 mg / kg, 0.0075 mg / kg, 0.01 mg / kg) on impulse decision in rats with high and low impulses were investigated. In the first experiment, rats were divided into high impulse group and low impulse group (8 rats in each group). There was a significant difference in the proportion of large reward selection between the two groups. In experiment 2, 0.05 mg 路kg ~ (-1) 路kg ~ (-1) O _ (5) mg 路kg ~ (-1) 路kg ~ (-1) ~ (-1) 路kg ~ (-1) 路kg ~ (-1 However, 0.075mg/kg oxytremor significantly increased the response time and missed reporting ratio in both groups. In experiment 3, 0.005 mg 路kg-1 mg / kg SCH23390 significantly inhibited the increase in the proportion of high-impulse reward selection induced by 0.05mg/kg oxytremor in rats. 0.0075mg/kg SCH23390 significantly enhanced the reduction of large reward selection in low impulse rats induced by 0.05mg/kg oxytremor. However, combined administration of 0.05mg/kg oxytremor and 0.01mg/kg SCH23390 significantly decreased the proportion of large reward (delayed 0s delivery) in both groups, and significantly increased the rate of underreporting in the high impulse group. The results showed that oxytremor could decrease the level of impulsive decision-making and increase the level of impulsive decision in low-impulse rats. SCH23390 could inhibit the reduction of impulsive decision-making in high-impulsive rats induced by oxytremor. Increase the level of impulsive decision-making induced by oxytremor in low-impulse rats. These results suggest that muscarinic choline can indirectly affect dopaminergic system and affect individual impulse decision level.
【学位授予单位】：首都师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：B848

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