Departamento de Farmacología y Toxicología, Facultad de Medicina; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM); Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas12); Instituto Universitario de Investigación en Neuroquímica UCM, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040, Madrid, Spain.
Departamento de Biología Molecular, Departamento de Neuropatología Molecular, Centro de Biología Molecular Severo Ochoa (UAM-CSIC); Red de Terapia Celular (TerCel), Universidad Autónoma de Madrid, C/ Nicolás Cabrera, 28049, Madrid, Spain.
Mol Neurobiol. 2019 Nov;56(11):7522-7533. doi: 10.1007/s12035-019-1619-x. Epub 2019 May 3.
The standard pharmacological treatment of the major depressive disorder (MDD) is still grounded in a monoaminergic approach. Consequently, antidepressant treatments pursue to heighten serotonergic and noradrenergic neurotransmissions. Thus, the aim of this study was to assess the impact of exposure to a well-characterized animal model, the chronic mild stress (CMS) on serotonin (5-HT) and noradrenaline (NE) levels, and reuptake transporters and receptors in the frontal cortex (FC) of CMS-exposed rats. Moreover, considering the diverse pharmacological profiles of existing antidepressants and the large number of patients not responding to treatments, we have investigated whether generally utilized antidepressants can modulate their expression. Male Wistar rats were exposed to CMS and some of them treated with desipramine, escitalopram, or duloxetine. Possible changes in the described monoaminergic neurotransmission elements were evaluated. CMS induced differences in the expression of reuptake transporters and receptors involved in the monoaminergic neurotransmission pointing towards the weakening of their signaling. CMS antidepressant-treated rats showed an improvement of the monoaminergic tone, being desipramine and duloxetine more influential than escitalopram over noradrenergic elements and having the three antidepressant-tested effects on serotonergic transmission. In summary, there are molecular alterations on the monoaminergic neurotransmission in FC induced by CMS exposure. Besides, antidepressant treatments modulate the elements of these neurotransmission systems differentially.
目前，治疗重度抑郁症（MDD）的标准药物治疗仍然基于单胺能方法。因此，抗抑郁药物的治疗旨在提高 5-羟色胺（5-HT）和去甲肾上腺素（NE）的神经传递。因此，本研究旨在评估暴露于一种经过充分研究的动物模型（慢性轻度应激（CMS））对 CMS 暴露大鼠额叶皮质（FC）中 5-HT 和 NE 水平及其再摄取转运体和受体的影响。此外，鉴于现有抗抑郁药的多种药理学特性以及大量对治疗无反应的患者，我们研究了一般使用的抗抑郁药是否可以调节其表达。雄性 Wistar 大鼠暴露于 CMS 中，其中一些大鼠用去甲丙咪嗪、依地普仑或度洛西汀治疗。评估了描述的单胺能神经递质传递元素的可能变化。CMS 诱导了参与单胺能神经传递的再摄取转运体和受体表达的差异，表明其信号转导减弱。CMS 抗抑郁治疗大鼠表现出单胺能神经递质的改善，去甲丙咪嗪和度洛西汀对去甲肾上腺素元素的影响比依地普仑更大，而三种测试的抗抑郁药对 5-HT 传递均有影响。总之，CMS 暴露会导致 FC 中单胺能神经递质传递的分子改变。此外，抗抑郁药物对这些神经递质系统的元素的调节作用不同。
