5-HT3 antagonists decrease discounting rate without affecting sensitivity to reward magnitude in the delay discounting task in mice
5-HT3 antagonists decrease discounting rate without affecting sensitivity to reward magnitude in the delay discounting task in mice
复制标题
5-HT3拮抗剂降低贴现率而不影响小鼠延迟贴现任务中对奖励大小的敏感性
DOI：
10.1007/s00213-018-4954-0
复制
发表时间：
2018
影响因子：
3.4
通讯作者：
Tanaka Kenji F.
中科院分区：
文献类型：
--
作者：
Mori Marina;Tsutsui-Kimura Iku;Mimura Masaru;Tanaka Kenji F.
啮齿动物的冲动选择通常是根据延迟折扣任务（DDT）中延迟大幅度选择的比例（%大选择）来评估的。然而，由于%大的选择是由两个敏感性，以增强幅度和敏感性延迟强化（即，贴现率），区别地评估这些贴现参数代表了一个关键问题，需要确定大鼠中每个参数的方法。众所周知，5-羟色胺（5-HT）系统与冲动选择有关;然而，只有少数研究区分了折扣参数并研究了5-HT调节剂如何影响折扣率。我们在小鼠中进行了贴现参数分析，并检查了各种5-HT modulators on discounting rate.MethodsWe set up DDTs with different delay scheduled to determine which scheduled could address delay-discounting rates in mice.我们研究了以下药物对冲动选择的影响：5-HT再摄取抑制剂（帕罗西汀），5-HT 1A受体激动剂（8-OH-DPAT），和两个5-HT 3受体拮抗剂（格拉司琼和昂丹司琼）。在较短而不是较长的时间表下，%大的选择遵循指数函数，并允许我们推导出贴现率。我们选择了一个DDT与4秒的延迟时间表进行进一步的实验。格拉司琼和昂丹司琼，但不是帕罗西汀或8-OH-DPAT，折扣率下降，而不影响敏感性的magnesium.ConclusionWe发现，一种方法来计算折扣率在大鼠也适用于小鼠模型。我们还提供了5-HT 3拮抗剂控制小鼠冲动选择的证据。
RationaleImpulsive choice has often been evaluated in rodents according to the proportion of choices for the delayed large magnitude reinforcer (%large choice) in a delay-discounting task (DDT). However, because %large choice is influenced by both sensitivity to reinforcer magnitude and sensitivity to delayed reinforcement (i.e., discounting rate), distinctively evaluating such discounting parameters represents a critical issue demanding methods to determine each parameter in rats. The serotonin (5-HT) system is well known to be involved in impulsive choice; nevertheless, only a few studies have distinguished discounting parameters and investigated how 5-HT modulators affect discounting rate.ObjectiveHere, we performed a discounting parameter analysis in mice and examined the effects of various 5-HT modulators on discounting rate.MethodsWe set up DDTs with different delay schedules to determine which schedule could address delay-discounting rates in mice. We examined the effect of the following drugs on impulsive choice: a 5-HT reuptake inhibitor (paroxetine), a 5-HT1Areceptor agonist (8-OH-DPAT), and two 5-HT3receptor antagonists (granisetron and ondansetron).ResultsMice showed typical delay discounting at the shorter delay schedules (up to 4 s delay). The %large choice under shorter, but not longer, schedules followed an exponential function and allowed us to derive discounting rates. We selected a DDT with a 4-s delay schedule for further experiments. Granisetron and ondansetron, but not paroxetine or 8-OH-DPAT, decreased discounting rates without affecting sensitivity to reinforcer magnitude.ConclusionWe found that a method to calculate discounting rates in rats is also applicable to mouse models. We also provided evidence that 5-HT3antagonism controls impulsive choice in mice.