Background

Zebrafish are growing in use as a model for understanding drug dependence and addiction. Sensitization paradigms have been a useful tool in identifying mechanisms involved in drug-induced behavioral and neurological changes, but in zebrafish have tended to focus on locomotor, rather than cognitive, endpoints.

Methods

Here, we used a novel method, the FMP Y-maze, which measures continuous performance through a series of repeated binary choices (L vs R), to establish a model for assessing parameters associated with psychostimulant-induced behavioral and cognitive sensitization in adult zebrafish.

Results

Repeat, intermittent exposure to d-amphetamine (AMPH) for 14 days increased alternations (LRLR) in the maze, suggesting improved working memory, which was enhanced further following drug challenge after a short withdrawal period, suggesting behavioral sensitization. However, this cognitive enhancement coincided with a reduction in the use of other exploration strategies, hypolocomotion, and inhibition of cognitive flexibility. Like AMPH, exposure to nicotine (NIC) increased alternations following drug challenge after chronic treatment. Repeat NIC exposure appeared to induce both cognitive and psychomotor sensitization, as evidenced by increased working memory performance (alternations) and locomotor activity, without negatively impacting other search strategies or cognitive flexibility.

Conclusion

Chronic treatment with AMPH or NIC boosts cognitive performance in adult zebrafish. Cognitive sensitization occurred with both drugs, resulting in enhanced working memory; however, repeat AMPH exposure, following a withdrawal period, resulted in inhibited cognitive flexibility, an effect not evident with repeat NIC exposure. Cognitive and behavioral sensitization paradigms in zebrafish could serve as a useful tool for assessing cognitive states which result in cognitive enhancing or impairing effects of drugs.

中文翻译：

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D-苯丙胺和尼古丁致敏对成年斑马鱼的认知和行为影响

背景

斑马鱼越来越多地用作理解药物依赖和成瘾的模型。敏化范式一直是确定药物引起的行为和神经学变化所涉及的机制的有用工具，但在斑马鱼中，它倾向于关注运动终点，而不是认知终点。

方法

在这里，我们使用了一种新方法 FMP Y 迷宫，它通过一系列重复的二元选择（L 对 R）来测量连续性能，以建立一个模型来评估与成年斑马鱼中精神兴奋剂引起的行为和认知敏化相关的参数.

结果

重复、间歇性地接触d-苯丙胺 (AMPH) 14 天会增加迷宫中的交替 (LRLR)，表明工作记忆得到改善，在短暂停药后药物激发后进一步增强，表明行为敏化。然而，这种认知增强与其他探索策略、运动减退和认知灵活性抑制的使用减少相吻合。与 AMPH 一样，接触尼古丁 (NIC) 会增加慢性治疗后药物激发后的交替。重复 NIC 暴露似乎会诱发认知和心理运动敏化，如工作记忆表现（交替）和运动活动增加所证明的那样，而不会对其他搜索策略或认知灵活性产生负面影响。

结论

使用 AMPH 或 NIC 进行慢性治疗可提高成年斑马鱼的认知能力。两种药物均发生认知敏化，导致工作记忆增强；然而，在停药期后重复暴露于 AMPH 会导致认知灵活性受到抑制，这种影响在重复暴露于 NIC 时不明显。斑马鱼的认知和行为致敏范式可以作为评估认知状态的有用工具，这些状态导致药物的认知增强或损害作用。