Ben-Shahar Osnat, Posthumus Eric J, Waldroup Stephanie A, Ettenberg Aaron
Department of Psychology, University of California, Santa Barbara, CA 93106-9660, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Apr 1;32(3):863-9. doi: 10.1016/j.pnpbp.2008.01.002. Epub 2008 Jan 11.
Rats allowed extended daily access (6 h) to cocaine, consume high doses of the drug and escalate their cocaine intake over days, resembling the pattern of cocaine use seen in human addicts. The current study was designed to test whether such animals would also demonstrate the heightened motivation to seek cocaine seen in human addicts. Rats were trained to lever press for i.v. cocaine (0.25 mg/infusion) over a 5-day period of 1 h sessions. Subjects were then assigned to either a brief-access (1 h/day) or an extended-access condition for an additional 10 days. Control rats lever pressed for i.v. saline. Following the final self-administration session animals were tested for their motivation to receive cocaine in an operant runway apparatus. Extended-access animals exhibited significantly higher motivation for cocaine in the runway (where they received 1.0 mg/kg cocaine i.v. upon goal-box entry) as was evident by faster run times and less ambivalence about entering the goal box (i.e. retreat behavior) than either brief-access or control subjects. Brief and extended-access animals, tested in the Elevated Plus Maze, exhibited comparable and significant increases in anxiety following a single 1.0 mg/kg i.v. injection of cocaine, as compared to saline control animals that were challenged with i.v. saline infusion. Together, these data suggest that extended access to cocaine results in an especially high motivation for the drug that is not accounted for by reductions in the anxiogenic properties of cocaine.
允许大鼠每天长时间（6小时）接触可卡因，它们会摄入高剂量的这种药物，并在数天内逐渐增加可卡因摄入量，这与人类成瘾者的可卡因使用模式相似。本研究旨在测试这类动物是否也会表现出人类成瘾者中所见的对可卡因寻求的增强动机。在为期5天、每天1小时的实验中，训练大鼠通过按压杠杆静脉注射可卡因（0.25毫克/次注射）。然后将实验对象分配到短期接触组（每天1小时）或长期接触组，再进行10天实验。对照大鼠通过按压杠杆静脉注射生理盐水。在最后一次自我给药实验后，使用操作性跑道装置测试动物接受可卡因的动机。长期接触组的动物在跑道中对可卡因表现出显著更高的动机（在进入目标箱时静脉注射1.0毫克/千克可卡因），这表现为与短期接触组或对照组相比，它们的奔跑时间更快，进入目标箱时的矛盾心理更少（即退缩行为）。在高架十字迷宫中进行测试时，与静脉注射生理盐水的对照动物相比，单次静脉注射1.0毫克/千克可卡因后，短期和长期接触组的动物均表现出相当且显著的焦虑增加。总之，这些数据表明，长时间接触可卡因会导致对该药物产生特别高的动机，而这并非可卡因致焦虑特性降低所导致的。
