Orsini Caitlin A, Mitchell Marci R, Heshmati Sara C, Shimp Kristy G, Spurrell Megan S, Bizon Jennifer L, Setlow Barry
Department of Psychiatry, University of Florida College of Medicine, P.O. Box 100256, Gainesville, FL, 32610-0256, United States.
Department of Psychiatry, Yale University School of Medicine, 1 Church St., Fl7, New Haven, CT, 06510, United States.
Behav Brain Res. 2017 Mar 15;321:130-136. doi: 10.1016/j.bbr.2017.01.001. Epub 2017 Jan 3.
Chronic administration of cocaine can cause pronounced and enduring cognitive alterations such as increases in impulsive choice. Chronic cocaine can also result in enhanced dopamine (DA) release in the nucleus accumbens (NAc) in response to reward-related cues. It is possible that this enhanced DA release in the NAc is a mechanism by which cocaine increases impulsive choice. To date, however, the specific role of DA in the NAc in impulsive choice is unclear. To begin to address this, rats received acute microinjections of the indirect DA agonist amphetamine directly into the NAc prior to testing in a delay discounting task in which rats chose between a small, immediate and a large, delayed food reward. When delays to the large reward increased within test sessions, amphetamine increased choice of the large reward. When delays decreased within test sessions, however, amphetamine decreased choice of the large reward. These findings suggest that, rather than specifically mediating impulsive choice, DA neurotransmission in the NAc is necessary for flexible adaptation of choice strategies in the presence of shifting reward contingencies. These results further indicate that enhancements in NAc DA release likely do not account for lasting increases in impulsive choice caused by chronic cocaine.
长期使用可卡因会导致明显且持久的认知改变,比如冲动选择增加。长期使用可卡因还会导致伏隔核(NAc)中多巴胺(DA)释放增强,以应对与奖励相关的线索。NAc中这种增强的DA释放可能是可卡因增加冲动选择的一种机制。然而,迄今为止,DA在NAc中对冲动选择的具体作用尚不清楚。为了开始解决这个问题,在一项延迟折扣任务测试前,给大鼠的NAc直接急性微量注射间接DA激动剂苯丙胺,在该任务中大鼠要在小的即时食物奖励和大的延迟食物奖励之间做出选择。当在测试过程中到大奖励的延迟增加时,苯丙胺增加了对大奖励的选择。然而,当在测试过程中延迟减少时,苯丙胺减少了对大奖励的选择。这些发现表明,NAc中的DA神经传递并非专门介导冲动选择,而是在奖励意外情况发生变化时灵活调整选择策略所必需的。这些结果进一步表明,NAc中DA释放的增强可能无法解释长期使用可卡因导致的冲动选择的持续增加。