雄性大鼠寻救行为的冲突模型
Summary
这一冲突模型用于测量接触成瘾药物后的抑制控制损伤, 或其他可能影响抑制控制的因素。性刺激和厌恶性障碍同时出现, 因此雄性老鼠必须克服障碍才能接近性奖励。
Abstract
本协议将一种新的冲突任务描述为大鼠抑制控制的模型。在这个模型中, 一个代表高价值奖励的自然奖励刺激 (性刺激) 和厌恶刺激 (引脚) 同时呈现。雄性老鼠必须爬或跳过充满别针的障碍, 才能接近并调查性伴侣。如果动物坚持在他们接近的行为, 而不管厌恶刺激, 它被认为是一个不适应或危险的寻求奖励的行为。冲突任务允许评估因接触吗啡等滥用药物或压力事件而造成的抑制控制不足。
这种模式的主要优点是, 它提供了一个简单而快速的方法来发现接触阿片类药物或其他压力事件后抑制控制的缺陷。除了阿片类药物, 这种行为模型还将有助于快速发现其他致瘾药物引起的抑制控制缺陷。然而, 限制因素是, 在这一冲突任务下, 雄性老鼠的表现可能会受到反复测试的效果。今后, 人们可以希望, 在修改这一冲突模型的基础上, 能够确定接触阿片类药物后具有寻求奖励行为的强迫性表型的个体。
Introduction
吸毒成瘾是一种慢性脑病, 其特点是冲动和强迫药物的寻求和服用1。成瘾的这些主要特征都被假设为抑制控制 2,3的能力受损, 即未能抑制立即追求奖励刺激, 从而发展出适应性不良行为模式4。
无通任务和停止信号任务是用来测量响应抑制能力 2,5的原型任务。这两种实验范式通过对比不常见的抑制反应与隐含的去基线 6,7来评估一个人抑制不适当的行为的能力。在这些任务中显示的反应抑制已被证明对可卡因使用者8,9、阿片剂成瘾者10和尼古丁使用者11有损害。另外两个任务–反转学习和多项选择串行反应时间任务–也提供了响应抑制/抑制控制 12,13的测量。然而, 在啮齿类动物身上进行的这些范式大多不仅需要长期的训练, 以便研究对象能够区分不同信号所代表的响应要求, 而且学习速度和学习效果的个体差异可能会干扰随后的抑制试验11的结果.
本文提出了一种新的冲突任务, 可用于测量接触致瘾药物后的抑制控制障碍。在这项任务中, 一个自然的奖励刺激 (性刺激), 代表一个高价值的奖励 14, 和厌恶刺激 (别针), 雄性老鼠必须征服, 同时提出。雄性老鼠必须爬或跳过充满别针的障碍, 才能接近并调查性伴侣。如果动物坚持其接近行为, 而不管厌恶刺激, 它被认为是一个不适应或危险的寻求奖励的行为。建立此任务的理由之一是, 它在概念上很简单, 不会像其他任务那样对执行过程提出很高的要求。与其他测量反应抑制的任务相比, 这种冲突任务是基于自然行为的, 具有正常性功能和性经验的老鼠可以在没有学习过程的情况下直接检测。另一个理由是, 在这项任务中提出的冲突在接近奖励和避免厌恶刺激 (或被刺中的风险) 之间可能有更好的效力, 因为它模仿吸毒成瘾者经常把自己放在类似的地方冲突, 但坚持追求毒品奖励, 无论现实生活中的消极后果的风险15。
因此, 应用这种冲突模型是一种快速而敏感的方法, 可以发现接触成瘾药物后抑制控制的缺陷, 或其他可能影响抑制控制能力的因素, 如压力。它还为研究抑制控制中潜在缺陷的神经机制提供了一种新的行为策略。此外, 还可以在此任务中添加其他修改。例如, 通过用社会刺激来取代性刺激来改变成本效益比率可以揭示出更多的行为意义。
Protocol
这项研究由中国科学院心理学研究所国际评论委员会 (irb) 批准, 所有实验均按照美国国立卫生研究院 (美国) 《实验动物护理和使用指南》 (2011年)。 1. 冲突模型的材料和设置 每个笼子里有四只老鼠 (50 厘米长 x 22.5 厘米宽 x 30 厘米高), 在可控温度 (22–25°c) 和一个反转的12小时光/暗周期 (21:30 亮起) 至少10天。请注意:在实验开始时, 分别使用了雄性和雌性 …
Representative Results
为了探讨这种冲突模型是否能揭示阿片类药物引起的不良就业风险寻求奖励的行为, 通过短期 (wd7) 后的 t 检验, 比较了含盐和吗啡预处理组表现出的寻奖行为。长期 (wd17) 分别从吗啡中撤出 (图 2)。结果表明, 在戒断的第7天和第17天, 吗啡预处理的大鼠的接近行为明显高于盐预处理大鼠 (图 2a:t=-3.958; d. f. = 24;p < 0.01。<strong cl…
Discussion
药物滥用18引起的抑制性控制缺陷对促进强制吸毒行为和复发19,20起具有重要作用。这里提出的冲突模型为探讨接触成瘾药物的个体抑制控制的变化提供了新的方法。
协议中有几个关键步骤。首先, 研究对象 (雄性老鼠) 在进入后续冲突任务之前必须获得性经验。例如, 雄性老鼠在药物治疗前需要通过交配筛查 (至少?…
Offenlegungen
The authors have nothing to disclose.
Acknowledgements
本论文得到了心理学研究所心理健康重点实验室 (klmh2016k01) 和创伤后应激患者人群评估与干预技术研究 (jcyj2017041313130301569) 的支持。
Materials
| Acetic acid | Beijing Tongguangjingxi Chemical company | CN No.81601 | CH3COOH |
| Benzypenicillin sodium for Injection | Huabei Pharmaceutical | F7072109 | C16H17N2NaO4S |
| Cotton swabs | Wan Xin, Shandong, China | 8 cm | |
| β-estradiol benzoate | SIGMA-ALDRICH | E8515-200MG | estradiol benzoate |
| Gauze | Wan Xin, Shandong, China | 21s × 21s 110×100 | |
| Hemostatic forceps | Beijing Zhong Sheng Wanda Biotechnology Co.,Ltd. | ||
| Morphine hydrochloride | Qinghai Pharmaceutical Co. Ltd | 20100105 | Morphine hydrochloride |
| Ophthalmic scissors | Beijing Zhong Sheng Wanda Biotechnology Co.,Ltd. | ||
| Pentobarbital Sodium | Sigma | C11H17O3N2Na | |
| Precision animal shocker | Coulbourn | ||
| Progesterone | SIGMA-ALDRICH | V900699-5G | progesterone |
| Sesama oil | Fengyi trading company ltd. | Sesama oil | |
| Sodium chloride injection | HuaLu Pharmaceutical | H17092107 | NaCl |
| Scalpels | Gillette | 96797241 | |
| Surgical blades | Shanghai Pudong Jinhuan Medical Products Co.,Ltd | ||
| Suture needles | Han Qin, Shanghai, China | Δ1/2 6×14 | |
| Silk sutures | Shanghai Pudong Jinhuan Medical Products Co.,Ltd | ||
| Sprague-Dawley rats | Vital River Animal Center, Beijing, China | Sprague-Dawley | animal strain |
| Syringe | WeiGao Group Medical Polymer Co.Ltd | 1ml, 2ml | |
| Tweezers | Beijing Zhong Sheng Wanda Biotechnology Co.,Ltd. |
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Diesen Artikel zitieren
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