Pesarico Ana Paula, Rosa Suzan G, Stangherlin Eluza C, Mantovani Anderson C, Zeni Gilson, Nogueira Cristina Wayne
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, Rio Grande do Sul, Brazil.
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, Rio Grande do Sul, Brazil.
J Psychiatr Res. 2017 Jun;89:28-37. doi: 10.1016/j.jpsychires.2017.01.013. Epub 2017 Jan 22.
7-Fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) is a promising isoquinoline that elicits an antidepressant-like action in rodents. In this study, an animal model of stress induced by maternal separation was used to investigate the effects of FDPI in Wistar rats of 30 and 90 days of age. It was investigated the effects of maternal separation in the self-care behavior and the contribution of glutamatergic and gamma-aminobutyric acid (GABA)ergic systems in the FDPI action. Male Wistar rats were separated from their mothers for 3 h/day from postnatal day (PND) 1-10. The rats were treated at different ages (PND-30 and PND-90) with FDPI (5 mg/kg, intragastrically/7 days) and performed the splash test. Maternal separation reduced total grooming time in the splash test, an index of motivational and self-care behavior, and FDPI treatment was effective in reversing this behavior in rats at both ages. The neurochemical parameters were differently affected, dependent on the age of rats, by maternal separation and FDPI. Maternal separation increased the GABA uptake and the excitatory amino acid transporter 1 levels in the prefrontal cortices of rats at PND-30 and FDPI was effective against these alterations. At PND-90, maternal separation decreased the glutamate uptake and increased the GABA uptake and the N-methyl-D-aspartate (NMDA) receptor 2B levels in the prefrontal cortices of rats. FDPI reversed the neurochemical alterations caused by maternal separation in the prefrontal cortices of rats at PND-90. The results of this study demonstrated that FDPI reversed the reduction in self-care behavior induced by maternal separation stress in rats by modulating the glutamatergic/GABAergic systems in rats.
7-氟-1,3-二苯基异喹啉-1-胺(FDPI)是一种有前景的异喹啉,在啮齿动物中可引发类似抗抑郁的作用。在本研究中,采用母婴分离诱导的应激动物模型,研究FDPI对30日龄和90日龄Wistar大鼠的影响。研究了母婴分离对自我护理行为的影响以及谷氨酸能和γ-氨基丁酸(GABA)能系统在FDPI作用中的贡献。雄性Wistar大鼠从出生后第1天至第10天每天与母亲分离3小时。在不同年龄(出生后第30天和第90天)用FDPI(5mg/kg,灌胃/每7天一次)处理大鼠,并进行溅水试验。母婴分离减少了溅水试验中的总梳理时间,这是动机和自我护理行为的一个指标,FDPI处理能有效逆转两个年龄组大鼠的这种行为。神经化学参数受到母婴分离和FDPI的不同影响,这取决于大鼠的年龄。母婴分离增加了出生后第30天大鼠前额叶皮质中GABA的摄取和兴奋性氨基酸转运体1的水平,而FDPI可有效对抗这些改变。在出生后第90天,母婴分离降低了大鼠前额叶皮质中谷氨酸的摄取,增加了GABA的摄取和N-甲基-D-天冬氨酸(NMDA)受体2B的水平。FDPI逆转了出生后第90天大鼠前额叶皮质中由母婴分离引起的神经化学改变。本研究结果表明,FDPI通过调节大鼠的谷氨酸能/GABA能系统,逆转了母婴分离应激诱导的大鼠自我护理行为减少。