Russell V, Allie S, Wiggins T
Department of Physiology, Faculty of Health Sciences, Medical School Observatory, University of Cape Town, 7925, Cape Town, South Africa.
Behav Brain Res. 2000 Dec 20;117(1-2):69-74. doi: 10.1016/s0166-4328(00)00291-6.
Spontaneously hypertensive rats (SHR) are used as a model for attention-deficit/hyperactivity disorder (ADHD) since SHR are hyperactive and they show defective sustained attention in behavioral tasks. Using an in vitro superfusion technique we showed that norepinephrine (NE) release from prefrontal cortex slices of SHR was not different from that of their Wistar-Kyoto (WKY) control rats when stimulated either electrically or by exposure to buffer containing 25 mM K(+). The monoamine vesicle transporter is, therefore, unlikely to be responsible for the deficiency in DA observed in SHR, since, in contrast to DA, vesicle stores of NE do not appear to be depleted in SHR. In addition, alpha(2)-adrenoceptor mediated inhibition of NE release was reduced in SHR, suggesting that autoreceptor function was deficient in prefrontal cortex of SHR. So, while DA neurotransmission appears to be down-regulated in SHR, the NE system appears to be under less inhibitory control than in WKY suggesting hypodopaminergic and hypernoradrenergic activity in prefrontal cortex of SHR. These findings are consistent with the hypothesis that the behavioral disturbances of ADHD are the result of an imbalance between NE and DA systems in the prefrontal cortex, with inhibitory DA activity being decreased and NE activity increased relative to controls.
自发性高血压大鼠（SHR）被用作注意力缺陷多动障碍（ADHD）的模型，因为SHR表现为多动，并且在行为任务中显示出持续注意力缺陷。使用体外灌流技术，我们发现，当通过电刺激或暴露于含有25 mM K(+)的缓冲液中时，SHR前额叶皮质切片中去甲肾上腺素（NE）的释放与它们的Wistar-Kyoto（WKY）对照大鼠没有差异。因此，单胺囊泡转运体不太可能是SHR中观察到的多巴胺（DA）缺乏的原因，因为与DA不同，SHR中NE的囊泡储存似乎没有耗尽。此外，SHR中α(2)-肾上腺素能受体介导的NE释放抑制作用减弱，这表明SHR前额叶皮质中的自身受体功能存在缺陷。所以，虽然SHR中的DA神经传递似乎下调，但NE系统似乎比WKY受到的抑制控制更少，这表明SHR前额叶皮质中存在多巴胺能功能减退和去甲肾上腺素能活性亢进。这些发现与以下假设一致，即ADHD的行为障碍是前额叶皮质中NE和DA系统失衡的结果，相对于对照，抑制性DA活性降低而NE活性增加。
