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安非他命、哌甲酯、托莫西汀和吗啡对大鼠在调整停止信号反应时间任务中反应的影响。

Effects of amphetamine, methylphenidate, atomoxetine, and morphine in rats responding under an adjusting stop signal reaction time task.

机构信息

Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX, 78229, USA.

Addiction Research, Treatment & Training Center of Excellence, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX, 78229, USA.

出版信息

Psychopharmacology (Berl). 2019 Jun;236(6):1959-1972. doi: 10.1007/s00213-019-5183-x. Epub 2019 Feb 23.

Abstract

RATIONALE

Stop signal reaction time procedures are used to investigate behavioral and neurobiological processes that contribute to behavioral inhibition and to evaluate potential therapeutics for disorders characterized by disinhibition and impulsivity. The current study examined effects of amphetamine, methylphenidate, atomoxetine, and morphine in rats responding under an adjusting stop signal reaction time task that measures behavioral inhibition, as well as motor impulsivity.

METHODS

Rats (n = 8) completed a two-response sequence to earn food. During most trials, responses following presentation of a visual stimulus (go signal) delivered food. Occasionally, a tone (stop signal) was presented signifying that food would be presented only if the second response was withheld. Responding after the stop signal measured inhibition and responding prior to the start of the trial (premature) measured motor impulsivity. Delay to presentation of the stop signal was adjusted for individual subjects based on performance.

RESULTS

Amphetamine and methylphenidate increased responding after presentation of the stop signal and markedly increased premature responding. Atomoxetine modestly improved accuracy on stop trials and decreased premature responding. Morphine did not alter stop trial accuracy or premature responding up to doses that decreased the number of trials initiated.

CONCLUSIONS

These data demonstrate the sensitivity of an adjusting stop signal reaction time task to a range of drug effects and shows that some drugs that enhance dopaminergic transmission, such as amphetamine, can differentially alter various types of impulsive behavior.

摘要

原理

停止信号反应时间程序用于研究有助于行为抑制的行为和神经生物学过程,并评估用于治疗以抑制和冲动为特征的障碍的潜在疗法。本研究在调整停止信号反应时间任务下检查了安非他命、哌甲酯、阿托西汀和吗啡对大鼠的影响,该任务测量行为抑制以及运动冲动性。

方法

大鼠(n=8)完成了两个反应序列以获取食物。在大多数试验中,视觉刺激(Go 信号)呈现后会进行响应,从而提供食物。偶尔,会发出一声音调(停止信号),表示只有在第二个响应被抑制的情况下才会提供食物。在停止信号呈现后进行响应测量抑制,在试验开始前进行响应(过早)测量运动冲动性。根据表现,为每个个体调整停止信号呈现的延迟。

结果

安非他命和哌甲酯增加了停止信号呈现后的响应,并显著增加了过早响应。阿托西汀适度提高了停止试验的准确性并减少了过早响应。吗啡在不减少起始试验次数的剂量下,不会改变停止试验的准确性或过早响应。

结论

这些数据表明,调整停止信号反应时间任务对一系列药物作用具有敏感性,并表明一些增强多巴胺能传递的药物,如安非他命,可以不同地改变各种类型的冲动行为。

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