Di Ciano Patricia, Pushparaj Abhiram, Kim Aaron, Hatch Jessica, Masood Talal, Ramzi Abby, Khaled Maram A T M, Boileau Isabelle, Winstanley Catherine A, Le Foll Bernard
Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, 33 Russell Street, Toronto, Canada M5S 2S1.
Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
PLoS One. 2015 Sep 9;10(9):e0136267. doi: 10.1371/journal.pone.0136267. eCollection 2015.
Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.
赌博是一种成瘾性疾病,会给社会和个人带来严重代价。迄今为止,尚无获批用于治疗赌博障碍的药物疗法。有证据表明多巴胺在赌博障碍中起作用,因此可能提供一个治疗靶点。因此,本研究旨在研究D2、D3和D4受体的选择性拮抗剂和激动剂在临床上使用的爱荷华赌博任务的啮齿动物类似物中的作用。在这个大鼠赌博任务(rGT)中,动物被训练将不同的反应孔与不同数量和概率的食物颗粒奖励以及惩罚性超时时间联系起来。与爱荷华赌博任务一样,最佳策略是避免诱人的高风险高回报选项,而是选择那些与每次试验较小奖励但惩罚也较低相关的选项,从而随着时间的推移最大化获得的奖励量。给予这些选择性配体不会影响rGT下的决策。只有D4药物对潜伏期测量有适度影响,表明D4可能在某种程度上有助于此任务下的决策。