Kantak Kathleen M, Udo Tomoko, Ugalde Francisco, Luzzo Christopher, Di Pietro Nina, Eichenbaum Howard B
Laboratory of Behavioral Neuroscience, Department of Psychology, Boston University, MA 02215, USA.
Psychopharmacology (Berl). 2005 Sep;181(2):227-36. doi: 10.1007/s00213-005-2243-1. Epub 2005 Oct 14.
Individuals who abuse cocaine have cognitive deficits, particularly in functions associated with the orbitofrontal cortex. It is not clear to what extent the impact of cocaine on cognitive functioning is related to its role as a behavioral reinforcer. A preclinical means to investigate this issue is to use a yoked-triad procedure in which sets of three animals either contingently self-administer cocaine or receive passive administration of cocaine or saline in a noncontingent manner.
Using this procedure, we assessed cocaine's effect on learning that requires a functionally intact prefrontal cortex (prelimbic or insular/orbital subregions) or hippocampus.
Rats self-administering 1-mg/kg unit doses of cocaine responded under a fixed-ratio 5, time-out 20-s schedule of drug delivery. Testing took place in a radial-arm maze within the first 30 min after 2-hr drug sessions ended, beginning after 2.5 months of cocaine or saline exposure.
Rats self-administering cocaine earned 14-18 infusions on average throughout different phases of the study. In groupwise comparisons, learning in the visually guided delayed win-shift (prelimbic prefrontal cortex-related) and win-shift (hippocampus-related) tasks was not influenced by contingent or noncontingent cocaine exposure. Session latency, though, was shorter in both cocaine-exposed groups during the win-shift task. During the odor-guided delayed win-shift task (insular/orbital prefrontal cortex-related), learning was disrupted in rats self-administering cocaine, with no influence of noncontingent cocaine exposure.
Based on these and previous findings, learning related to functioning of the insular/orbital prefrontal cortex and amygdala is the most consistently disrupted in cocaine-intoxicated rats after long-term drug exposure.
滥用可卡因的个体存在认知缺陷，尤其是在与眶额叶皮质相关的功能方面。目前尚不清楚可卡因对认知功能的影响在多大程度上与其作为行为强化剂的作用有关。研究这个问题的一种临床前方法是采用配对三联体程序，即每组三只动物，其中一组动物可自主给药可卡因，另外两组动物则以非配对的方式被动给予可卡因或生理盐水。
采用该程序，我们评估了可卡因对需要功能完整的前额叶皮质（边缘前区或岛叶/眶区亚区）或海马体参与的学习的影响。
自行给药1毫克/千克单位剂量可卡因的大鼠，在固定比率为5、给药间隔20秒的药物递送时间表下做出反应。在2小时的药物给药期结束后的前30分钟内，在放射状迷宫中进行测试，测试在可卡因或生理盐水暴露2.5个月后开始。
在整个研究的不同阶段，自行给药可卡因的大鼠平均获得14 - 18次注射。在分组比较中，视觉引导延迟赢-转换任务（与边缘前区前额叶皮质相关）和赢-转换任务（与海马体相关）中的学习不受配对或非配对可卡因暴露的影响。不过，在赢-转换任务中，两个可卡因暴露组的给药潜伏期均较短。在气味引导延迟赢-转换任务（与岛叶/眶区前额叶皮质相关）中，自行给药可卡因的大鼠的学习受到干扰，非配对可卡因暴露对此没有影响。
基于这些以及之前的研究结果，长期药物暴露后，可卡因中毒大鼠中与岛叶/眶区前额叶皮质和杏仁核功能相关的学习受到的干扰最为一致。
