Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Blindern, NO-0317 Oslo, Norway.
Behav Brain Funct. 2011 Mar 30;7:6. doi: 10.1186/1744-9081-7-6.
ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR.
The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness.
The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness.
The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing.
ADHD 目前被定义为一种认知/行为发育障碍，所有临床标准均为行为标准。多动、冲动和注意力不集中目前被认为是主要的临床症状。目前没有生物学标志物，但有大量证据表明，ADHD 行为与涉及额叶的神经元回路中多巴胺能和去甲肾上腺素能调节不良有关。目前验证效果最好的 ADHD 动物模型——自发性高血压大鼠（SHR）表现出明显的多动、冲动和注意力持续时间不足。本研究的主要目的是研究慢性低剂量安非他命对 SHR 中类似 ADHD 症状的行为影响。
本研究测试了 0.75 和 2.2mg/kg 腹腔注射 l-安非他命碱对雄性 SHR 及其对照品，即 Wistar Kyoto 大鼠（WKY）的行为影响。通过视觉辨别任务来测试类似 ADHD 的行为，该任务可测量多动、冲动和注意力不集中。
在基线条件下，SHR 表现出明显的冲动、多动和注意力不集中，而慢性给予 l-安非他命治疗后，这些行为得到改善。然而，不同行为的剂量反应曲线有所不同。最显著的是，0.75mg/kg 的 l-安非他命剂量改善了注意力不集中，而没有减少多动和冲动。2.2mg/kg 的剂量改善了注意力不集中，同时减少了 SHR 的多动和冲动。
在 14 天的每日给药过程中，l-安非他命降低 SHR 中 ADHD 行为症状的效果得以维持，没有出现耐受性发展的迹象。
