Viana Glauce Socorro de Barros, Xavier Cecilia Coelho, do Vale Eduardo Mulato, Lopes Maria Janice Pereira, Alves Viviane de Jesus, Costa Roberta de Oliveira, Neves Kelly Rose Tavares
Faculty of Medicine Estácio of Juazeiro do Norte, Ceará, Brazil.
Faculty of Medicine of the Federal University of Ceará, Ceará, Brazil.
IBRO Rep. 2017 Dec 2;4:7-13. doi: 10.1016/j.ibror.2017.11.001. eCollection 2018 Jun.
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 10 mg/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.
氯胺酮（KET）是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，其快速有效的抗抑郁作用已得到研究，甚至对难治性抑郁症也有疗效。尽管抑郁症是全球致残的主要原因，但治疗可以是可行、可负担且具有成本效益的，从而减轻人群健康负担。我们评估了KET的抗抑郁样作用及其对单胺含量（多巴胺及其代谢产物以及5-羟色胺）和酪氨酸羟化酶（TH）的影响。此外，还评估了多巴胺转运体（DAT）和5-羟色胺转运体（SERT，分别为多巴胺和5-羟色胺转运体）。雄性瑞士小鼠分为对照组和KET治疗组。动物经KET（2、5或10mg/kg，腹腔注射）急性处理后，进行强迫游泳试验，以评估抗抑郁样行为。丙咪嗪和氟西汀用作对照。结果表明，KET剂量依赖性地减少了不动时间，试验后不久，将动物安乐死以进行纹状体解剖和单胺测定。此外，对大脑（纹状体、海马体和前额叶皮质）进行免疫组织化学处理，以检测TH、DAT和SERT。KET高剂量组可增加小鼠纹状体中多巴胺及其代谢产物（3,4-二羟基苯乙酸和高香草酸）以及主要是5-羟色胺的含量，这些作用与TH增加和DAT免疫反应性降低有关。此外，在纹状体和海马体中观察到SERT免疫反应性降低。结果表明，KET的抗抑郁样作用可能除其他因素外还涉及单胺能途径，纹状体TH免疫反应性增加以及脑多巴胺（DAT）和5-羟色胺（SERT）转运体减少表明了这一点。
