Center for Neuroscience at the University of Pittsburgh, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
J Neurosci. 2011 Mar 30;31(13):4926-34. doi: 10.1523/JNEUROSCI.5426-10.2011.
Cocaine users display a wide range of cognitive impairments. Because treatment outcome is dependent on baseline cognitive ability, it is clinically important to understand the underlying neurobiology of these deficits. Therefore, it is crucial to determine whether cocaine exposure by itself is an etiological factor and, if so, to determine the overall nature of cognitive deficits associated with cocaine use. This will help to guide therapeutic approaches that address cognitive components of cocaine use to improve treatment outcome. We used rhesus monkeys in a longitudinal study in which 14 animals were characterized before assignment to matched control (n = 6) and cocaine self-administration (n = 8) groups. Self-administration took place on 4 consecutive days/week over 9 months, with a maximum (and typical) daily cumulative intake of 3.0 mg/kg. Weekly cognitive assessments (total of 36) were conducted after a 72 h drug-free period. We used a stimulus discrimination task with reversal to evaluate associative learning and the cognitive control/flexibility needed to adapt to changes in reward contingencies. After extended self-administration, initial accuracy on the stimulus discrimination indicated intact associative learning. However, animals were impaired at maintaining high levels of accuracy needed to reach criterion and initiate the reversal. Increasing the reward contrast between stimuli permitted evaluation of reversal performance and revealed striking deficits in the cocaine group. Impairments in visual working memory were also observed using a delayed match-to-sample task. These results suggest a combination of generalized, possibly attentional, impairments, along with a more specific cognitive control impairment implicating orbitofrontal cortex dysfunction.
可卡因使用者表现出广泛的认知障碍。由于治疗效果取决于基线认知能力，因此了解这些缺陷的潜在神经生物学机制在临床上非常重要。因此，确定可卡因暴露本身是否是一个病因因素，以及如果是，确定与可卡因使用相关的认知缺陷的总体性质，这一点至关重要。这将有助于指导针对可卡因使用认知成分的治疗方法，以提高治疗效果。我们使用恒河猴进行了一项纵向研究，其中 14 只动物在被分配到匹配的对照组（n = 6）和可卡因自我给药组（n = 8）之前进行了特征描述。自我给药在 9 个月内连续 4 天/周进行，每日最大（和典型）累积摄入量为 3.0mg/kg。每周进行一次认知评估（共 36 次），在 72 小时无药物期后进行。我们使用具有反转的刺激辨别任务来评估联想学习以及适应奖励条件变化所需的认知控制/灵活性。在延长的自我给药后，刺激辨别任务的初始准确性表明存在完整的联想学习。然而，动物在维持达到标准和开始反转所需的高准确性方面存在障碍。增加刺激之间的奖励对比可以评估反转表现，并在可卡因组中发现明显的缺陷。使用延迟匹配样本任务也观察到视觉工作记忆的损伤。这些结果表明存在一般化的、可能是注意力的损伤，以及更特定的认知控制损伤，涉及眶额叶皮层功能障碍。
