Noseda Ana Carolina D, Rodrigues Lais S, Targa Adriano D S, Aurich Mariana F, Vital Maria A B F, Da Cunha Cláudio, Lima Marcelo M S
Laboratório de Neurofisiologia, Departamento de Fisiologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Behav Brain Res. 2014 Dec 15;275:136-45. doi: 10.1016/j.bbr.2014.09.007. Epub 2014 Sep 9.
It has been observed that the secretion pattern of melatonin is modified in Parkinson's disease (PD). Hence, it is hypothesized that dysregulations of melatonin MT2 receptors may be involved in the installation of depression in PD patients. Together with recent evidence based on the use of the intranigral rotenone model of PD, have led to the hypothesis that modulating the striatal MT2 receptor could provide a more comprehensive understanding of the antidepressant properties triggered. To further investigate this issue, male Wistar rats were infused with intranigral rotenone (12μg/μL) and seven days later subjected to a rapid eye movement sleep deprivation (REMSD) for 24h. After, we injected within the striatum the MT2 selective agonist, 8-M-PDOT (10μg/μL), the MT2 selective antagonist, 4-P-PDOT (5μg/μL) or vehicle. Subsequently, they were tested in the forced swimming test and were allowed to perform the sleep rebound (REB). Then, the rats were re-tested, and the striatum, hippocampus and substantia nigra pars compacta (SNpc) were collected for neurochemical purposes. Results indicated substantial antidepressant effects promoted by the blockade of striatal MT2 receptors that were potentiated by REMSD. MT2 activation increased DA levels in the striatum and hippocampus, while MT2 blockade increase DA in the SNpc. 4-P-PDOT treatment of the rotenone REMSD group generated a decrement in 5-HT levels within the striatum, hippocampus and SNpc. However, increased 5-HT turnover was observed among these structures. Therefore, we demonstrated the neurochemical antidepressant effect induced by striatal MT2 blockage associated with REMSD in the rotenone model of PD.
据观察，帕金森病（PD）患者褪黑素的分泌模式会发生改变。因此，有人推测褪黑素MT2受体的失调可能与PD患者抑郁症的发生有关。结合最近基于PD黑质内注射鱼藤酮模型的证据，提出了调节纹状体MT2受体可能有助于更全面理解引发的抗抑郁特性这一假说。为进一步研究此问题，给雄性Wistar大鼠黑质内注射鱼藤酮（12μg/μL），7天后对其进行24小时快速眼动睡眠剥夺（REMSD）。之后，在纹状体内注射MT2选择性激动剂8 - M - PDOT（10μg/μL）、MT2选择性拮抗剂4 - P - PDOT（5μg/μL）或溶剂。随后，对它们进行强迫游泳试验，并让其进行睡眠反弹（REB）。然后，对大鼠再次进行测试，并收集纹状体、海马和黑质致密部（SNpc）用于神经化学研究。结果表明，纹状体MT2受体阻断促进了显著的抗抑郁作用，且REMSD可增强这种作用。MT2激活可增加纹状体和海马中的多巴胺（DA）水平，而MT2阻断则可增加SNpc中的DA水平。鱼藤酮REMSD组用4 - P - PDOT治疗后，纹状体、海马和SNpc内5 - 羟色胺（5 - HT）水平降低。然而，在这些结构中观察到5 - HT周转率增加。因此，我们证明了在PD鱼藤酮模型中，与REMSD相关的纹状体MT2阻断诱导的神经化学抗抑郁作用。
