Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Neurochem Res. 2014 May;39(5):825-32. doi: 10.1007/s11064-014-1275-5. Epub 2014 Mar 15.
Spontaneously hypertensive rats (SHRs) are used as a model for attention-deficit/hyperactivity disorder (ADHD), since SHRs are hyperactive and show defective sustained attention in behavioral tasks. The psychostimulants amphetamine and methylphenidate and the selective norepinephrine reuptake inhibitor atomoxetine are used as ADHD medications. The effects of high K(+) stimulation or psychostimulants on brain norepinephrine or dopamine release in SHRs have been previously studied both in vitro and in vivo, but the effects of atomoxetine on these neurotransmitters have not. The present study examined the effects of administration of atomoxetine on extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex of juvenile SHRs and Wistar-Kyoto (WKY) rats. Baseline levels of prefrontal norepinephrine, dopamine, and serotonin were similar in SHRs and WKY rats. Systemic administration of atomoxetine (3 mg/kg) induced similar increases in prefrontal norepinephrine and dopamine, but not serotonin, levels in both strains. Furthermore, there was no difference in high K(+)-induced increases in extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex between SHRs and WKY rats. These findings indicate that monoamine systems in the prefrontal cortex are similar between SHRs and WKY rats.
自发性高血压大鼠（SHRs）被用作注意缺陷多动障碍（ADHD）的模型，因为 SHRs 表现出多动和在行为任务中注意力持续缺陷。安非他命、哌甲酯和选择性去甲肾上腺素再摄取抑制剂托莫西汀等精神兴奋剂被用作 ADHD 药物。先前已经在体外和体内研究了高 K+刺激或精神兴奋剂对 SHRs 大脑去甲肾上腺素或多巴胺释放的影响，但尚未研究托莫西汀对这些神经递质的影响。本研究检查了托莫西汀给药对幼年 SHRs 和 Wistar-Kyoto（WKY）大鼠前额皮质细胞外去甲肾上腺素、多巴胺和 5-羟色胺水平的影响。SHRs 和 WKY 大鼠的前额皮质去甲肾上腺素、多巴胺和 5-羟色胺的基础水平相似。全身给予托莫西汀（3mg/kg）可引起两种品系的前额皮质去甲肾上腺素和多巴胺水平相似的增加，但 5-羟色胺水平没有增加。此外，SHRs 和 WKY 大鼠前额皮质中高 K+诱导的细胞外去甲肾上腺素、多巴胺和 5-羟色胺水平的增加没有差异。这些发现表明 SHRs 和 WKY 大鼠前额皮质中的单胺系统相似。
