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哌甲酯而非西酞普兰,可减少执行时间折扣任务的大鼠的冲动性选择。

Methylphenidate, but not citalopram, decreases impulsive choice in rats performing a temporal discounting task.

作者信息

Koloski Miranda F, Terry Alyssa, Lee Noelle, Ramanathan Dhakshin S

机构信息

Mental Health, VA San Diego Medical Center, San Diego, CA, United States.

Center of Excellence for Stress and Mental Health, VA San Diego Medical Center, San Diego, CA, United States.

出版信息

Front Psychiatry. 2024 May 8;15:1385502. doi: 10.3389/fpsyt.2024.1385502. eCollection 2024.

Abstract

INTRODUCTION

Drugs targeting monoamine systems remain the most common treatment for disorders with impulse control impairments. There is a body of literature suggesting that drugs affecting serotonin reuptake and dopamine reuptake can modulate distinct aspects of impulsivity - though such tests are often performed using distinct behavioral tasks prohibiting easy comparisons.

METHODS

Here, we directly compare pharmacologic agents that affect dopamine (methylphenidate) vs serotonin (citalopram) manipulations on choice impulsivity in a temporal discounting task where rats could choose between a small, immediate reward or a large reward delayed at either 2 or 10s. In control conditions, rats preferred the large reward at a small (2s) delay and discounted the large reward at a long (10s) delay.

RESULTS

Methylphenidate, a dopamine transport inhibitor that blocks reuptake of dopamine, dose-dependently increased large reward preference in the long delay (10s) block. Citalopram, a selective serotonin reuptake inhibitor, had no effect on temporal discounting behavior. Impulsive behavior on the temporal discounting task was at least partially mediated by the nucleus accumbens shell. Bilateral lesions to the nucleus accumbens shell reduced choice impulsivity during the long delay (10s) block. Following lesions, methylphenidate did not impact impulsivity.

DISCUSSION

Our results suggest that striatal dopaminergic systems modulate choice impulsivity via actions within the nucleus accumbens shell, whereas serotonin systems may regulate different aspects of behavioral inhibition/impulsivity.

摘要

引言

针对单胺系统的药物仍然是治疗冲动控制障碍最常用的方法。有大量文献表明,影响5-羟色胺再摄取和多巴胺再摄取的药物可以调节冲动性的不同方面——尽管此类测试通常使用不同的行为任务进行,难以进行简单比较。

方法

在此,我们在一个时间折扣任务中直接比较影响多巴胺(哌甲酯)与5-羟色胺(西酞普兰)的药物对选择冲动性的影响,在该任务中大鼠可以在一个小的即时奖励或一个延迟2秒或10秒的大奖励之间进行选择。在对照条件下,大鼠在小延迟(2秒)时更喜欢大奖励,而在长延迟(10秒)时则对大奖励进行折扣。

结果

哌甲酯是一种多巴胺转运抑制剂,可阻止多巴胺的再摄取,它在长延迟(10秒)组中剂量依赖性地增加了对大奖励的偏好。西酞普兰是一种选择性5-羟色胺再摄取抑制剂,对时间折扣行为没有影响。时间折扣任务中的冲动行为至少部分由伏隔核壳介导。双侧损毁伏隔核壳可减少长延迟(10秒)组中的选择冲动性。损毁后,哌甲酯不影响冲动性。

讨论

我们的结果表明,纹状体多巴胺能系统通过伏隔核壳内的作用调节选择冲动性,而5-羟色胺系统可能调节行为抑制/冲动性的不同方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9ab/11109432/ff598f3bfd03/fpsyt-15-1385502-g001.jpg

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