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首页> 外文期刊>IBRO Reports >The monoaminergic pathways and inhibition of monoamine transporters interfere with the antidepressive-like behavior of ketamine
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The monoaminergic pathways and inhibition of monoamine transporters interfere with the antidepressive-like behavior of ketamine

机译：单胺能途径和单胺转运蛋白的抑制干扰氯胺酮的抗抑郁样行为

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Ketamine (KET), a NMDA receptor antagonist, has been studied for its rapid and efficacious antidepressant effect, even for the treatment-resistant depression. Although depression is a major cause of disability worldwide, the treatment can be feasible, affordable and cost-effective, decreasing the population health burden. We evaluated the antidepressive-like effects of KET and its actions on monoamine contents (DA and its metabolites, as well as 5-HT) and on tyrosine hydroxylase (TH). In addition DAT and SERT (DA and 5-HT transporters, respectively) were also assessed. Male Swiss mice were divided into Control and KET-treated groups. The animals were acutely treated with KET (2, 5 or 10mg/kg, i.p.) and subjected to the forced swimming test, for evaluation of the antidepressive-like behavior. Imipramine and fluoxetine were used as references. The results showed that KET decreased dose-dependently the immobility time and shortly after the test, the animals were euthanized for striatal dissections and monoamine determinations. In addition, the brain (striata, hippocampi and prefrontal cortices) was immunohistochemically processed for TH, DAT and SERT. KET at its higher dose increased DA and its metabolites (DOPAC and HVA) and mainly 5-HT contents, in mice striata, effects associated with increases in TH and decreases in DAT immunoreactivities. Furthermore, reductions in SERT immunoreactivities were observed in the striatum and hippocampus. The results indicate that KET antidepressive-like effect probably involves, among other factors, monoaminergic pathways, as suggested by the increased striatal TH immunoreactivity and reduced brain DA (DAT) and 5-HT (SERT) transporters.
机译：氯胺酮（KET）是一种NMDA受体拮抗剂，已被研究出其快速有效的抗抑郁作用，甚至用于抗药性抑郁症。尽管抑郁症是全球范围内致残的主要原因，但这种治疗方法可行，负担得起且具有成本效益，从而减轻了人口健康负担。我们评估了KET的抗抑郁样作用及其对单胺含量（DA及其代谢产物以及5-HT）和酪氨酸羟化酶（TH）的作用。此外，还评估了DAT和SERT（分别为DA和5-HT转运蛋白）。将雄性瑞士小鼠分为对照组和KET治疗组。用KET（2、5或10mg / kg，腹膜内）急性处理动物，并进行强迫游泳试验，以评估其抗抑郁样行为。使用丙咪嗪和氟西汀作为参考。结果表明，KET剂量依赖性地降低了固定时间，试验后不久，对动物进行安乐死以进行纹状体解剖和单胺测定。此外，对大脑（纹状体，海马和前额叶皮层）进行了免疫组织化学处理，以检测TH，DAT和SERT。在小鼠纹状体中，较高剂量的KET可增加DA及其代谢产物（DOPAC和HVA）以及主要是5-HT的含量，其作用与TH升高和DAT免疫反应性降低有关。此外，在纹状体和海马中观察到SERT免疫反应性降低。结果表明，如纹状体TH免疫反应性增加以及脑DA（DAT）和5-HT（SERT）转运蛋白降低所表明的那样，KET抗抑郁样作用可能涉及单胺能途径。

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