Pharmacological characterisation of the effort for reward task as a measure of motivation for reward in male mice.

Motivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats. However, mice currently offer a greater genetic toolkit to study risk genes and phenotypic models. Despite this, there is limited characterisation of their behaviour in this type of motivation task. Here, we investigate the effort for reward (EfR) task as a measure of motivational state in mice using drugs previously shown to modulate effort-based decision-making in rats and humans. Using male C57bl/6j mice, we test the effects of drugs which modulate DA transmission. We also test the effects of CP101-606 which does not act directly via DA modulation but has been shown to exert beneficial effects on motivational state. Finally, we test the sensitivity of the task to a chronic corticosterone (CORT) treatment. Amphetamine, methylphenidate, and CP101606 in mice increased high-effort responses for high-value reward, while administration of haloperidol decreased high-effort responses. Surprisingly, tetrabenazine had no effect at the doses tested. Chronic, low-dose CORT consumption did not alter task performance. These data suggest that the EfR task is sensitive to acute dopaminergic modulation and NR2B selective antagonism in mice. However, it may lack sensitivity to non-acute phenotypic models. Further work is required to demonstrate the utility of the task in this context. The online version contains supplementary material available at 10.1007/s00213-023-06420-9.

动机缺陷是多种精神疾病和神经退行性疾病共有的常见症状。基于努力的决策任务是一种可用于评估动机状态的可转化方法。该任务的大部分临床前验证来自对大鼠的急性药理学操作。然而，小鼠目前提供了更强大的基因工具包来研究风险基因和表型模型。尽管如此，在这种类型的动机任务中，对小鼠行为的特征描述有限。 在此，我们利用先前已表明可调节大鼠和人类基于努力的决策的药物，研究奖励努力（EfR）任务作为小鼠动机状态的一种衡量方法。 我们使用雄性C57bl/6j小鼠，测试调节多巴胺（DA）传递的药物的效果。我们还测试了CP101 - 606的效果，它不直接通过多巴胺调节起作用，但已被证明对动机状态有有益影响。最后，我们测试了该任务对慢性皮质酮（CORT）处理的敏感性。 在小鼠中，安非他明、哌甲酯和CP101606增加了对高价值奖励的高努力反应，而氟哌啶醇的给药则减少了高努力反应。令人惊讶的是，丁苯那嗪在测试剂量下没有效果。慢性低剂量皮质酮摄入没有改变任务表现。 这些数据表明，EfR任务对小鼠的急性多巴胺能调节和NR2B选择性拮抗敏感。然而，它可能对非急性表型模型缺乏敏感性。需要进一步的工作来证明该任务在这种情况下的实用性。 网络版包含补充材料，可在10.1007/s00213 - 023 - 06420 - 9获取。