Heal D J, Smith S L, Kulkarni R S, Rowley H L
RenaSci Consultancy Limited, BioCity, Nottingham NG1 1GF, UK.
Pharmacol Biochem Behav. 2008 Aug;90(2):184-97. doi: 10.1016/j.pbb.2008.03.016. Epub 2008 Apr 1.
Attention deficit hyperactivity disorder (ADHD) is a common childhood psychiatric condition that is effectively treated by catecholaminergic drugs with a variety of different mechanisms and the SH rat is frequently used as a model of this disorder. In vivo microdialysis in freely-moving rats has been employed extensively to provide a better understanding of the pharmacodynamics of drugs at their sites of action. In this review, these three topics are brought together to explore the contribution of in vivo microdialysis studies in spontaneously hypertensive (SH) rats to our understanding of the neurochemical deficits in this rat strain and the actions of ADHD drugs on catecholaminergic function in the prefrontocortex (PFC), striatum and nucleus accumbens. What is revealed is that basal efflux of norepinephrine in the PFC is attenuated, whilst striatal and mesolimbic dopaminergic neurotransmission is hyperfunctional; the latter observation fits closely with the hyperactive phenotype of the SH rat. Furthermore, experiments performed with the enantiomers of amphetamine and threo-methylphenidate demonstrate that pharmacodynamic effects of drugs reported from experiments in outbred rat strains, e.g. Sprague-Dawleys, do not necessarily translate to the SH rat. When the findings are compared with the clinical efficacy of drugs used in treating ADHD, they indicate that the most efficacious drugs powerfully increase both norepinephrinergic and dopaminergic neurotransmission.
注意缺陷多动障碍（ADHD）是一种常见的儿童精神疾病，可通过多种不同作用机制的儿茶酚胺能药物有效治疗，SH大鼠常被用作该疾病的模型。在自由活动的大鼠中进行体内微透析已被广泛应用，以更好地了解药物在其作用部位的药效学。在这篇综述中，将这三个主题结合起来，探讨在自发性高血压（SH）大鼠中进行的体内微透析研究对我们理解该大鼠品系神经化学缺陷以及ADHD药物对前额叶皮质（PFC）、纹状体和伏隔核中儿茶酚胺能功能作用的贡献。研究发现，PFC中去甲肾上腺素的基础外流减弱，而纹状体和中脑边缘多巴胺能神经传递功能亢进；后一观察结果与SH大鼠的多动表型密切相符。此外，用苯丙胺和苏式甲基苯丙胺的对映体进行的实验表明，在远交系大鼠品系（如Sprague-Dawleys大鼠）实验中报道的药物药效学效应不一定适用于SH大鼠。当将这些发现与用于治疗ADHD的药物的临床疗效进行比较时，结果表明最有效的药物能有力地增强去甲肾上腺素能和多巴胺能神经传递。
