Department of Psychology, Louisiana State University, Baton Rouge, LA, 70803, USA.
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Psychopharmacology (Berl). 2020 Dec;237(12):3783-3794. doi: 10.1007/s00213-020-05655-0. Epub 2020 Sep 22.
Methylphenidate and d-amphetamine, medications used for treatment of attention deficit hyperactivity disorder (ADHD), are used recreationally and self-administered by laboratory animals. Benztropine (BZT) analogs, like those medications, increase synaptic dopamine levels but are less effective in maintaining self-administration, suggesting clinical utility with less abuse liability.
The current study was designed to evaluate potential therapeutic effects of BZT analogs related to ADHD.
Rats responded under a delay-discounting procedure in which responses on one lever produced immediate delivery of a single food pellet and alternative responses produced four food pellets either immediately or with various temporal delays, with those delays arranged in ascending or random orders in different groups of rats. Selection of the smaller more immediate reinforcer has been suggested as an aspect of "impulsivity," a trait with suggested involvement in ADHD. Other rats were studied under fixed-interval (FI) 300-s schedules to assess drug effects on behavior under temporal control.
d-Amphetamine, methylphenidate, and the BZT analog AHN 1-055, but not AHN 2-005 or JHW 007, increased selection of the large, delayed reinforcer with either arrangement of delays. All drugs changed the temporal distribution of responses within the FI from one with responses concentrated at the end to a more uniform distribution. Changes in the temporal distribution of FI responding occurred with drugs that did not affect discounting suggesting that discounting does not arise directly from the same temporal control processes controlling FI responding.
AHN 1-055 may be of clinical utility in the treatment of ADHD.
哌醋甲酯和苯丙胺，用于治疗注意力缺陷多动障碍（ADHD）的药物，被娱乐性地使用，并被实验室动物自行管理。苯扎托品（BZT）类似物与这些药物一样，增加突触多巴胺水平，但在维持自我给药方面效果较差，这表明它们具有较少的滥用倾向和更大的临床应用价值。
本研究旨在评估 BZT 类似物与 ADHD 相关的潜在治疗效果。
大鼠在延迟折扣程序下进行反应，其中一个杠杆上的反应立即产生单个食物丸的传递，而替代反应则立即产生四个食物丸，或者在不同组的大鼠中以不同的时间延迟传递，这些延迟以递增或随机顺序排列。选择较小的、更即时的强化物被认为是“冲动”的一个方面，这种特质被认为与 ADHD 有关。其他大鼠在固定间隔（FI）300 秒的时间表下进行研究，以评估药物对时间控制下行为的影响。
d-苯丙胺、哌醋甲酯和 BZT 类似物 AHN 1-055，但不是 AHN 2-005 或 JHW 007，增加了大、延迟强化物的选择，无论延迟的安排如何。所有药物都改变了 FI 反应的时间分布，从反应集中在末端的分布变为更均匀的分布。FI 反应的时间分布的变化发生在不影响折扣的药物中，这表明折扣不是直接来自控制 FI 反应的相同时间控制过程。
AHN 1-055 可能在治疗 ADHD 方面具有临床应用价值。
