Feduccia Allison A, Duvauchelle Christine L
College of Pharmacy, Division of Pharmacology and Toxicology, University of Texas at Austin, USA.
J Vis Exp. 2010 Aug 20(42):1998. doi: 10.3791/1998.
Animal models of reinforcement have proven to be useful for understanding the neurobiological mechanisms underlying drug addiction. Operant drug self-administration and conditioned place preference (CPP) procedures are expansively used in animal research to model various components of drug reinforcement, consumption, and addiction in humans. For this study, we used a novel approach to studying drug reinforcement in rats by combining traditional CPP and self-administration methodologies. We assembled an apparatus using two Med Associate operant chambers, sensory stimuli, and a Plexiglas-constructed neutral zone. These modifications allowed our experiments to encompass motivational aspects of drug intake through self-administration and drug-free assessment of drug/cue conditioning strength with the CPP test. In our experiments, rats self-administered cocaine (0.75 mg/kg/inj, i.v.) during either four (e.g., the "short-term") or eight (e.g., the "long-term") alternating-day sessions in an operant environment containing distinctive sensory cues (e.g., olfactory and visual). On the alternate days, in the other (differently-cued) operant environment, saline was available for self-infusion (0.1 ml, i.v.). Twenty-four hours after the last self-administration/cue-pairing session, a CPP test was conducted. Consistent with typical CPP findings, there was a significant preference for the chamber associated with cocaine self-administration. In addition, in animals undergoing the long-term experiment, a significant positive correlation between CPP magnitude and the number of cocaine-reinforced lever responses. In conclusion, this apparatus and approach is time and cost effective, can be used to examine a wide array of topics pertaining to drug abuse, and provides more flexibility in experimental design than CPP or self-administration methods alone.
强化作用的动物模型已被证明有助于理解药物成瘾背后的神经生物学机制。操作性药物自我给药和条件性位置偏爱（CPP）程序在动物研究中被广泛用于模拟人类药物强化、消费和成瘾的各个组成部分。在本研究中，我们采用了一种新方法，通过结合传统的CPP和自我给药方法来研究大鼠的药物强化作用。我们使用两个Med Associate操作性条件反射箱、感觉刺激和一个由有机玻璃构建的中性区域组装了一套装置。这些改进使我们的实验能够通过自我给药涵盖药物摄入的动机方面，并通过CPP测试对药物/线索条件作用强度进行无药物评估。在我们的实验中，大鼠在含有独特感觉线索（如嗅觉和视觉）的操作性环境中，在四个（如“短期”）或八个（如“长期”）交替日的实验阶段自我注射可卡因（0.75毫克/千克/注射，静脉注射）。在交替日，在另一个（有不同线索的）操作性环境中，大鼠可以自我注射生理盐水（0.1毫升，静脉注射）。在最后一次自我给药/线索配对实验24小时后，进行CPP测试。与典型的CPP研究结果一致，大鼠对与可卡因自我给药相关的实验箱有显著偏好。此外，在进行长期实验的动物中，CPP强度与可卡因强化的杠杆反应次数之间存在显著正相关。总之，这种装置和方法具有时间和成本效益，可用于研究与药物滥用相关的广泛主题，并且比单独的CPP或自我给药方法在实验设计上提供了更大的灵活性。
