Effect of drugs of abuse on reward-based decision-making in rodents

在目前的研究中，我们开发了一种针对啮齿动物的赌博测试，使用放射臂迷宫来解决药物依赖患者的决策问题。在成本/收益决策任务中，大鼠从四只手臂中选择一只[一只低风险/低回报(LL)手臂，一只高风险/高收益(HH)手臂和两只空手臂]。这项测试包括每天连续16次试验。经过广泛的测试，幼稚的大鼠表现出选择行为，这取决于手臂的奖赏概率和奖赏价值。在长期使用甲基苯丙胺治疗后，这些动物比盐水处理的对照组大鼠更频繁地选择HH手臂。赌博实验后，与生理盐水对照组大鼠相比，甲基苯丙胺依赖大鼠的岛叶皮质、纹状体和伏隔核中c-Fos的表达明显增加。我们的发现表明，慢性甲基苯丙胺治疗可能会导致基于奖励的决策的改变。从岛叶皮质到纹状体的皮质-纹状体通路的异常激活可能与甲基苯丙胺依赖大鼠基于奖赏的决策障碍有关。

In the present study, we developed a gambling testfor rodents using a radial-arm maze to address the issue of decision-making in patients with drug dependence. Rats were trained in the cost/benefit decision-making task, in which they chose one of four arms [one low risk/low return (LL) arm, one high risk/high return (HH) arm and two empty arms]. The test consisted of consecutive 16 trials a day. Following extensive testing, naive rats showed the choice behavior, which is dependent on reward probability and reward value of the arms. Following chronic treatment with methamphetamine, the animals chose HH arms more frequently than did saline-treated control rats. After the gambling test, c-Fos expression was markedly increased in the insular cortex, striatum, and nucleus accumbens of methamphetamine-dependent rats compared to saline-treated control rats. Our findings suggest that chronic methamphetamine treatment may lead to alternations of reward-based decision-making. Aberrant activation of the cortico-striatal pathway from insular cortex to striatum may be associated with the impairment of reward-based decision-making in methamphetamine-dependent rats.