Knackstedt Lori A, Samimi Max M, Ettenberg Aaron
Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, CA 93106, USA.
Pharmacol Biochem Behav. 2002 Jul;72(4):931-6. doi: 10.1016/s0091-3057(02)00764-5.
The affective response to cocaine (COC) has been suggested to follow a time-course and pattern that adheres to the prediction of opponent-process models of drug actions. While the initial impact of the drug is positive, within a few minutes that effect wanes and is replaced by an aversive state characterized by anxiety and drug craving. We have demonstrated this phenomenon in animals by showing that rats prefer distinctive environments associated with the immediate effects of intravenous COC (1.0 mg/kg) but avoid environments associated with the state present 15-min postinjection. Human addicts have reported taking ethanol with their COC as a means of attenuating the negative aftereffects of COC administration. The combination of ethanol and COC results in the production of cocaethylene (CE), a metabolite of COC having psychostimulant properties. The current study was devised to assess whether the immediate and delayed affective responses to CE might account for the self-medication strategy of COC addicts pretreating themselves with ethanol. Rats developed conditioned place preferences for environments paired with the immediate effects of a 1.44-mg/kg intravenous dose of CE (equimolar to a 1.0-mg/kg dose of COC). While no aversive effects were observed at 0, 5, or 15 min postinjection, reliable place avoidance was detected for an environment paired with the internal state present 30-min post-CE. These data are consistent with the view that the development of CE may account for efficacy of ethanol to delay and weaken the aversive aftereffects of COC.
对可卡因（COC）的情感反应被认为遵循一种时间进程和模式，这与药物作用的对抗过程模型的预测相符。虽然药物的初始影响是积极的，但在几分钟内这种效果就会减弱，并被一种以焦虑和药物渴望为特征的厌恶状态所取代。我们通过实验证明，大鼠更喜欢与静脉注射COC（1.0毫克/千克）的即时效果相关的独特环境，但会避开与注射后15分钟时出现的状态相关的环境。人类成瘾者报告说会在服用COC时同时摄入乙醇，以此来减轻服用COC后的负面后效应。乙醇和COC的组合会产生可卡乙碱（CE），它是具有精神兴奋特性的COC的一种代谢产物。本研究旨在评估对CE的即时和延迟情感反应是否可以解释COC成瘾者用乙醇进行自我治疗的策略。大鼠对与静脉注射1.44毫克/千克剂量的CE（与1.0毫克/千克剂量的COC等摩尔）的即时效果配对的环境产生了条件性位置偏好。虽然在注射后0、5或15分钟未观察到厌恶效应，但在与CE注射后30分钟时出现的内部状态配对的环境中检测到了可靠的位置回避。这些数据与以下观点一致，即CE的产生可能解释了乙醇延迟和减弱COC厌恶后效应的功效。
