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.

译文

锂和丙戊酸盐都是公认的双相情感障碍治疗方法。研究还发现,锂能有效减少情绪障碍患者的自杀行为。冲动是双相情感障碍和自杀行为的有效内表型。我们评估了锂或丙戊酸盐治疗对先前显示出相对较高水平的认知冲动的选择性繁殖小鼠的认知冲动的影响。在延迟折扣范式中对小鼠进行训练,该范式是一种认知冲动的度量,反映了对即时性的行为偏见,然后用锂,丙戊酸盐或对照食物进行治疗。经过3周的药物治疗后,对小鼠进行了各种延迟测试,以获得较大的延迟奖励。在此期间继续进行药物治疗。锂降低了冲动性,而丙戊酸盐对选择行为没有影响。两种药物都增加了选择试验的数量和增强剂的摄入量,但是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,这是第一项证明锂降低认知冲动作用的研究。未来的研究可能集中在对有双相情感障碍或自杀风险的患者进行推定的药物疗法的能力,以改变这种疾病的冲动选择维度。

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