Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249.
Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249
J Neurosci. 2019 Feb 13;39(7):1249-1260. doi: 10.1523/JNEUROSCI.1721-18.2018. Epub 2018 Dec 17.
The costs associated with obtaining illicit drugs can fluctuate depending upon the relative drug availability. As a consequence of the changing costs, the effort that one must exert to obtain drugs is dynamic. Considerable evidence illustrates a critical role for dopamine in the ventral medial striatum in mediating drug reinforcement. However, little is known regarding how dopamine release is affected by changes in the costs associated with earning drugs. We used fast-scan cyclic voltammetry to determine how changes in the operant requirement affected dopamine release to self-administered cocaine in male rats. Dopamine release to cocaine infusions increased across trials during self-administration sessions using a fixed-ratio reinforcement schedule with a low operant requirement. However, increasing the operant requirement abolished the within-session elevation in dopamine release to drug rewards. This effect was not due to underlying changes in preinfusion dopamine levels and was not explained by cocaine levels in the brain. This within-session increase in dopamine release to cocaine infusions reemerged when the operant requirement was lowered. Under a progressive ratio reinforcement schedule, there was no increase in dopamine release to drug rewards across trials, which contrasts with prior studies demonstrating an increase in dopamine release to food rewards. Collectively, these findings illustrate that the influence of operant costs on reward-evoked dopamine release depends upon type of reward that can be earned (e.g., food or drug). The mesolimbic dopamine system is involved with mediating drug reinforcement. Although the costs associated with earning drugs are dynamic, no studies to date have examined how dopamine release to drug rewards is affected by changing costs. By performing fast-scan cyclic voltammetry recordings in rats self-administering cocaine, the present work demonstrates that changing the operant costs reversibly modulates the dopamine response to cocaine rewards. Furthermore, these findings highlight that the influence of costs on dopamine release to drug rewards differs from the established effect of costs on dopamine release to food rewards.
获得非法药物的相关成本会根据相对药物供应情况而波动。由于成本的变化，获得药物所需的努力是动态的。大量证据表明，多巴胺在腹侧被盖区中起关键作用，介导药物强化。然而，对于与获得药物相关的成本变化如何影响多巴胺释放，人们知之甚少。我们使用快速扫描循环伏安法来确定操作要求的变化如何影响可卡因自我给药的雄性大鼠中多巴胺的释放。在使用低操作要求的固定比率强化方案进行自我给药期间，多巴胺释放到可卡因输注的量在整个试验中增加。然而，增加操作要求会消除药物奖励过程中多巴胺释放的日内升高。这种效应不是由于预输注多巴胺水平的潜在变化引起的，也不能用大脑中的可卡因水平来解释。当操作要求降低时，可卡因输注引起的多巴胺释放日内增加再次出现。在递增比率强化方案下，药物奖励的多巴胺释放没有随着试验的进行而增加，这与先前的研究表明多巴胺释放到食物奖励增加形成对比。总之，这些发现表明，操作成本对奖励引发的多巴胺释放的影响取决于可获得的奖励类型（例如，食物或药物）。中脑边缘多巴胺系统参与介导药物强化。尽管获得药物的相关成本是动态的，但迄今为止没有研究检查多巴胺释放到药物奖励的变化如何受到变化成本的影响。通过在自我给予可卡因的大鼠中进行快速扫描循环伏安记录，本工作表明，改变操作成本可可逆地调节多巴胺对可卡因奖励的反应。此外，这些发现强调了成本对药物奖励的多巴胺释放的影响与成本对食物奖励的多巴胺释放的既定影响不同。
