Schoenbaum Geoffrey, Saddoris Michael P, Ramus Seth J, Shaham Yavin, Setlow Barry
University of Maryland School of Medicine, Department of Anatomy and Neurobiology, 685 West Baltimore Street, HSF-1 Rm 280K, Baltimore, MD 21201, USA.
Eur J Neurosci. 2004 Apr;19(7):1997-2002. doi: 10.1111/j.1460-9568.2004.03274.x.
Addictive drugs, such as cocaine, cause long-lasting neural changes in prefrontal cortex. It has been hypothesized that these changes affect the behavioural control mediated by orbitofrontal cortex. To test this hypothesis, rats were given injections of cocaine (30 mg/kg/d, i.p.) or vehicle for 14 days and then trained after a 2-week withdrawal period in an odor discrimination task sensitive to the effects of orbitofrontal cortex lesions. We found that cocaine-treated rats, who demonstrated long-lasting sensitization to the locomotor activating effects of cocaine, failed to show normal changes in response latency during discrimination learning and were also slower than controls to acquire serial reversals. These behavioural impairments are identical to the effects of orbitofrontal cortex lesions in this task and show that cocaine exposure in rats can cause long-lasting effects on orbitofrontal-dependent functions. Notably, these effects were not correlated with increases in locomotor activity linked to cocaine-induced psychomotor sensitization observed before or after training, suggesting that the brain changes underlying the behavioural effects in the discrimination task are different from those mediating psychomotor sensitization.
成瘾性药物，如可卡因，会在前额叶皮层引起持久的神经变化。据推测，这些变化会影响眶额叶皮层介导的行为控制。为了验证这一假设，给大鼠注射可卡因（30毫克/千克/天，腹腔注射）或赋形剂，持续14天，然后在为期2周的戒断期后，在对眶额叶皮层损伤效应敏感的气味辨别任务中进行训练。我们发现，对可卡因的运动激活效应表现出持久敏感的可卡因处理大鼠，在辨别学习过程中反应潜伏期未能表现出正常变化，并且在获得连续反转方面也比对照组慢。这些行为障碍与该任务中眶额叶皮层损伤的效应相同，表明大鼠接触可卡因会对依赖眶额叶的功能产生持久影响。值得注意的是，这些效应与训练前后观察到的与可卡因诱导的精神运动敏感化相关的运动活动增加无关，这表明辨别任务中行为效应背后的大脑变化与介导精神运动敏感化的变化不同。
