Beardsley P.M., Anthony E.W., Lopez O.T.
G.D. Searle & Co., 4901 Searle Parkway, Skokie, Illinois, USA.
Behav Pharmacol. 1992 Oct;3(5):497-505.
Long-Evans hooded rats were initially trained to lever press, in standard, operant conditioning chambers, according to a fixed-ratio 1 (FR1) reinforcement schedule using 0.06ml deliveries of 8% w/v ethanol as the reinforcer, during daily Monday-Friday, 1h experimental sessions. Next, experimental sessions were reduced to 0.5h, the FR value was increased to 5, and the rats were trained to discriminate 2.0mg/kg s.c. phencyclidine (PCP) from saline vehicle using standard, drug discrimination training procedures, with 8% ethanol as the reinforcer. Following training, dose-response tests with PCP (0.1-4.0mg/kg), ketamine (0.1-18mg/kg), dexoxadrol (1.0-5.6mg/kg) and morphine (1.0-9.0mg/kg) were conducted. More PCP-lever presses were emitted than saline-lever presses at several doses of PCP, ketamine, and dexoxadrol, indicating generalization from the 2.0mg/kg PCP stimulus. When morphine was tested, more saline-lever than PCP-lever presses were made, and percent PCP-lever pressing never exceeded an average of 12% at any dose tested. This study demonstrates that one drug of abuse, PCP, can serve as a discriminative stimulus when another drug of abuse, ethanol, serves as the reinforcing stimulus, and is the first explicit laboratory demonstration of drug discriminative stimulus control during drug self-administration.
将Long-Evans有帽大鼠最初置于标准的操作性条件反射箱中进行杠杆按压训练,按照固定比率1(FR1)强化程序,使用0.06毫升8%(重量/体积)乙醇作为强化物,在周一至周五每天1小时的实验时段进行训练。接下来,将实验时段缩短至0.5小时,将FR值提高到5,并使用标准的药物辨别训练程序,以8%乙醇作为强化物,训练大鼠区分皮下注射2.0毫克/千克苯环己哌啶(PCP)和生理盐水。训练后,对PCP(0.1 - 4.0毫克/千克)、氯胺酮(0.1 - 18毫克/千克)、右吗拉胺(1.0 - 5.6毫克/千克)和吗啡(1.0 - 9.0毫克/千克)进行剂量反应测试。在几个PCP、氯胺酮和右吗拉胺剂量下,大鼠按压PCP杠杆的次数多于按压生理盐水杠杆的次数,表明从2.0毫克/千克PCP刺激产生了泛化。当测试吗啡时,大鼠按压生理盐水杠杆的次数多于按压PCP杠杆的次数,并且在任何测试剂量下,按压PCP杠杆的百分比从未超过平均12%。本研究表明,当一种滥用药物乙醇作为强化刺激时,另一种滥用药物PCP可以作为辨别刺激,并且这是药物自我给药过程中药物辨别刺激控制的首个明确的实验室证明。