Grilly D M, Loveland A
Psychology Department, Cleveland State University, OH 44115, USA.
Psychopharmacology (Berl). 2001 Jan 1;153(2):155-69. doi: 10.1007/s002130000580.
Because of the amphetamines' abuse potential and capability of exacerbating or inducing mood and psychotic disturbances, investigations of the behavioral effects of amphetamines commonly involve non-human animals, with the laboratory rat being by far the most common species used. Although investigators of the behavioral effects of amphetamine in rats sometimes refer to doses used as being "low", "moderate", "high", etc., it is not clear in what sense these terms apply.
To develop an operational definition of a low dose of amphetamine in rats, we reviewed studies that assessed the behavioral effects of dextroamphetamine (d-AMP) in rats in which some subset of doses, administered SC, IM or IP, was described as being "low". We then used the results of these studies to establish what the lowest effective dose ranges were across a variety of behavioral domains and compared these doses and their effects with those obtained with normal, healthy adult humans.
While the range of the lowest doses used in the studies with rats was quite broad (0.025-2.0 mg/kg), the median lowest effective doses observed (in the studies using doses of 0.125 mg/kg or less) were between 0.125 and 0.165 mg/kg across the behavioral domains of consummatory behavior, unconditioned or spontaneous behavior, learned behavior, and drug discriminative control. This range of doses was also found to be comparable to the lowest behaviorally effective doses of d-AMP (SC or PO) in normal human adults, which suggests that the sensitivity to the behavioral effects of amphetamine in these two species is fairly comparable.
Because of their ability to alter a wide variety of behaviors in rats, we conclude that low doses of d-AMP are in the 0.1-0.4 mg/kg range. Doses within this range typically: 1) constitute the ED50 in most drug discrimination/generalization procedures; 2) increase a variety of consummatory behaviors; 3) increase a variety of unconditioned or spontaneous motor activities; 4) increase low rate schedule-controlled behavior while exerting variable effects on high rate schedule controlled behavior; and 5) improve performance on some choice tasks, particularly those requiring sustained attention. Our analyses also indicate that, with respect to behavior, investigators do not always agree on what constitutes a low dose of amphetamine in rats and that doses assumed to be low for this species often are relatively high.
由于苯丙胺类药物具有滥用潜力，且能够加剧或诱发情绪及精神障碍，因此对苯丙胺类药物行为效应的研究通常涉及非人类动物，其中实验室大鼠是迄今为止最常用的物种。尽管研究大鼠中苯丙胺行为效应的研究人员有时会提及所使用的剂量为“低”、“中”、“高”等，但这些术语在何种意义上适用并不明确。
为了制定大鼠低剂量苯丙胺的操作性定义，我们回顾了评估右旋苯丙胺（d-AMP）对大鼠行为效应的研究，其中一些通过皮下注射、肌肉注射或腹腔注射给药的剂量子集被描述为“低”。然后，我们利用这些研究结果确定了各种行为领域中最低有效剂量范围，并将这些剂量及其效应与正常、健康成年人类获得的剂量及其效应进行了比较。
虽然在大鼠研究中使用的最低剂量范围相当广泛（0.025 - 2.0毫克/千克），但在摄食行为、非条件或自发行为、学习行为和药物辨别控制等行为领域中观察到的最低有效剂量中位数（在使用0.125毫克/千克或更低剂量的研究中）在0.125至0.165毫克/千克之间。还发现这个剂量范围与正常成年人类中d-AMP（皮下注射或口服）的最低行为有效剂量相当，这表明这两个物种对苯丙胺行为效应的敏感性相当。
由于它们能够改变大鼠的多种行为，我们得出结论，低剂量的d-AMP在0.1 - 0.4毫克/千克范围内。该范围内的剂量通常：1）在大多数药物辨别/泛化程序中构成半数有效剂量（ED50）；2）增加多种摄食行为；3）增加多种非条件或自发运动活动；4）增加低频率程序控制行为，同时对高频率程序控制行为产生可变影响；5）改善某些选择任务的表现，特别是那些需要持续注意力的任务。我们的数据还表明，在行为方面，研究人员对于大鼠中什么构成低剂量苯丙胺并不总是一致，并且对于该物种被认为是低剂量的情况，其剂量往往相对较高。
