Lithium, but not Valproate, Reduces Impulsive Choice in the Delay-Discounting Task in Mice
Lithium, but not Valproate, Reduces Impulsive Choice in the Delay-Discounting Task in Mice
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DOI：
10.1038/npp.2013.89
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发表时间：
2013-09-01
影响因子：
7.6
通讯作者：
Grahame, Nicholas J.
中科院分区：
文献类型：
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作者：
Halcomb, Meredith E.;Gould, Todd D.;Grahame, Nicholas J.
锂和丙戊酸盐都是治疗双相情感障碍的成熟疗法。研究还发现，锂在减少情绪障碍患者的自杀行为方面是有效的。冲动是双相情感障碍和自杀行为的一种有效的内在表型。我们评估了锂或丙戊酸盐对选择性繁殖的小鼠认知冲动的影响，这些小鼠以前被证明表现出相对较高的认知冲动水平。小鼠接受了延迟折扣范式的训练，这是一种反映即时行为偏差的认知冲动指标，然后用锂盐、丙戊酸盐或对照食物进行治疗。在药物治疗3周后，小鼠在不同的延迟时间进行测试，以获得大的、延迟的奖励。在此期间，药物治疗仍在继续。锂降低了冲动，而丙戊酸盐对选择行为没有影响。这两种药物都增加了选择试验的次数和增强剂的摄入量，但对选择行为的影响并不取决于这些动机的变化。据我们所知，这是第一个证明锂可以降低认知冲动的研究。未来的研究可能侧重于针对双相情感障碍或自杀风险患者的假定药物疗法是否能够改变这种疾病的冲动选择维度。
Both lithium and valproate are well-established treatments for bipolar disorder. Studies have also found that lithium is effective at reducing suicidal behaviors in patients with mood disorders. Impulsivity is a validated endophenotype of both bipolar disorder and suicidal behavior. We assessed effects of treatment with lithium or valproate on cognitive impulsivity in selectively bred mice previously shown to manifest relatively high levels of cognitive impulsivity. Mice were trained in the delay-discounting paradigm, a measure of cognitive impulsivity reflecting a behavioral bias towards immediacy, and then treated with lithium, valproate, or control chow. After 3 weeks of drug treatment, mice were tested at various delays to a large, delayed reward. Drug treatment continued during this time. Lithium reduced impulsivity, whereas valproate had no effect on choice behavior. Both drugs increased the number of choice trials and reinforcer intake, but effects on choice behavior did not depend on these motivational changes. To our knowledge, this is the first study demonstrating lithium's effects to reduce cognitive impulsivity. Future studies may focus on the ability of putative pharmacotherapies for patients at risk for bipolar disorder or suicide to modify the impulsive choice dimension of this diseases.