Calu Donna J, Stalnaker Thomas A, Franz Theresa M, Singh Teghpal, Shaham Yavin, Schoenbaum Geoffrey
Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Learn Mem. 2007 Apr 27;14(5):325-8. doi: 10.1101/lm.534807. Print 2007 May.
Drug addicts make poor decisions. These decision-making deficits have been modeled in addicts and laboratory animals using reversal-learning tasks. However, persistent reversal-learning impairments have been shown in rats and monkeys only after noncontingent cocaine injections. Current thinking holds that to represent the human condition effectively, animal models of addiction must utilize self-administration procedures in which drug is earned contingently; thus, it remains unclear whether reversal-learning deficits caused by noncontingent cocaine exposure are relevant to addiction. To test whether reversal learning deficits are caused by contingent cocaine exposure, we trained rats to self-administer cocaine, assessed cue-induced cocaine seeking in extinction tests after 1 and 30 d of withdrawal, and then tested for reversal learning more than a month later. We found robust time-dependent increases in cue-induced cocaine seeking in the two extinction tests (incubation of craving) and severe reversal-learning impairments.
吸毒成瘾者会做出糟糕的决策。这些决策缺陷已在成瘾者和实验动物中通过反转学习任务进行了模拟。然而，只有在非条件性注射可卡因后，大鼠和猴子才出现持续的反转学习损伤。目前的观点认为，为了有效模拟人类情况，成瘾的动物模型必须采用药物是通过条件性获得的自我给药程序；因此，尚不清楚非条件性接触可卡因导致的反转学习缺陷是否与成瘾相关。为了测试反转学习缺陷是否由条件性接触可卡因引起，我们训练大鼠自我给药可卡因，在戒断1天和30天后的消退试验中评估线索诱导的可卡因觅求，然后在一个多月后测试反转学习。我们发现在两次消退试验中，线索诱导的可卡因觅求呈强烈的时间依赖性增加（渴望的潜伏期），并且存在严重的反转学习损伤。
