Meil W.M., See R.E.
Department of Psychology, Washington State University, Pullman, WA 99164-4820 USA.
Behav Pharmacol. 1996 Dec;7(8):754-763.
The present study investigated the ability of drug-associated cues to reinstate extinguished responding following an extended period of withdrawal from cocaine self-administration. Rats self-administered cocaine (0.33mg/infusion) for 2 weeks of daily 3-h limited-access sessions under a fixed-interval (FI) schedule of reinforcement, in which responding resulted in simultaneous illumination of a stimulus light and drug infusions. Rats were then exposed to 20 daily extinction sessions. Noncontingent presentation of the stimulus light and infusion pump sound on day 21 of extinction resulted in a significant increase in responding. Twenty days later (43 days after cocaine withdrawal), rats returned to the operant chamber and exposed to drug-associated cues responded significantly more than animals exposed to extinction conditions. In a second experiment, using a form of variable-interval schedule in which the stimulus light was presented prior to drug infusions, stimulus-cued recovery of responding was similar to that obtained under the FI schedule. A third experiment showed that noncontingent presentation of the stimulus light alone on day 21 failed to reinstate extinguished responding, suggesting that stimulus-cued reinstatement of responding was due to a compound stimulus or preferential conditioning of the infusion pump sound. The present paradigm may serve as a useful model for the investigation of drug abuse and relapse, since it allows for the independent examination of the reinforcing and conditioned effects of a drug.
本研究调查了与药物相关的线索在长期戒除可卡因自我给药后恢复消退反应的能力。大鼠在固定间隔（FI）强化程序下，每天进行3小时有限接触时段的可卡因自我给药（0.33毫克/输注），持续2周，在此期间，反应会导致刺激光同时亮起和药物输注。然后大鼠接受20天的每日消退训练。在消退训练的第21天，非条件性呈现刺激光和输注泵声音导致反应显著增加。20天后（可卡因戒断43天后），返回操作箱并暴露于与药物相关线索的大鼠的反应明显多于暴露于消退条件下的动物。在第二个实验中，采用一种可变间隔程序形式，在药物输注前呈现刺激光，反应的刺激线索恢复与在FI程序下获得的相似。第三个实验表明，在第21天仅非条件性呈现刺激光未能恢复消退反应，这表明反应的刺激线索恢复是由于复合刺激或输注泵声音的优先条件作用。由于该范式允许独立检验药物的强化和条件作用效果，因此它可能成为研究药物滥用和复发的有用模型。
