Olsen Christopher M, Winder Danny G
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA.
Psychopharmacology (Berl). 2006 Jul;187(1):13-21. doi: 10.1007/s00213-006-0388-1. Epub 2006 Apr 27.
Drug self-administration is a powerful method to measure the reinforcing effects of a drug, as well as to investigate behavioral, biochemical, and physiological effects of a drug specific to contingent delivery. With the spectrum of genetically modified mice available, there is a need for well-designed drug self-administration studies tailored for rapid completion of studies in mice.
We set out to develop a methodology in mice for obtaining high levels of cocaine self-administration during the first exposure to the drug.
C57Bl/6J mice were trained to lever press for liquid reinforcer on a fixed ratio 1, then a progressive ratio (PR) schedule of reinforcement before intravenous self-administration of cocaine on a PR schedule.
Within a single 16-h session, each mouse self-administered either saline or 0.1, 0.3, 0.6, or 1.2 mg kg(-1) infusion(-1) of cocaine during four distinct 4-h subsessions. Mice showed a strong preference for cocaine vs saline, as demonstrated by higher breakpoints and greater preference for the active lever. Likewise, there was a dose-dependent increase in breakpoints obtained and in drug intake. Finally, animals receiving noncontingent cocaine pressed significantly less than mice self-administering the same dose of cocaine, indicating that a significant amount of active lever pressing is driven by drug-seeking and not the psychomotor-activating effects of cocaine alone.
Mice will reach high breakpoints and cocaine intake during an initial exposure to cocaine. This method is well-suited to rapidly obtain progressive ratio cocaine self-administration in mice.
药物自我给药是一种强大的方法，可用于测量药物的强化作用，以及研究特定于偶然给药的药物的行为、生化和生理效应。随着基因改造小鼠种类的不断增加，需要设计出精心的药物自我给药研究，以便在小鼠中快速完成研究。
我们着手开发一种在小鼠中获得首次接触药物时高水平可卡因自我给药的方法。
将C57Bl/6J小鼠训练在固定比率1下按压杠杆以获取液体强化物，然后在按渐进比率（PR）强化程序进行静脉注射可卡因自我给药之前，先按PR强化程序进行训练。
在单个16小时的实验期间，每只小鼠在四个不同的4小时时间段内自我给药生理盐水或0.1、0.3、0.6或1.2mg·kg⁻¹·注射⁻¹的可卡因。小鼠对可卡因的偏好明显高于生理盐水，表现为更高的断点和对活动杠杆的更大偏好。同样，获得的断点和药物摄入量呈剂量依赖性增加。最后，接受非偶然可卡因给药的动物按压杠杆的次数明显少于自我给药相同剂量可卡因的小鼠，这表明大量的活动杠杆按压是由觅药行为驱动的，而不仅仅是可卡因的精神运动激活作用。
小鼠在首次接触可卡因时会达到高断点和可卡因摄入量。这种方法非常适合在小鼠中快速获得渐进比率的可卡因自我给药。
