Zimmermann Fernanda Francine, Gaspary Karina Vidarte, Siebel Anna Maria, Bonan Carla Denise
Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.
Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Avenida Senador Attílio Fontana, 591E, 89809-000 Chapecó, SC, Brazil.
Behav Brain Res. 2016 Sep 15;311:368-374. doi: 10.1016/j.bbr.2016.05.059. Epub 2016 May 28.
Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia.
社会行为的改变发生在多种神经精神疾病中，如精神分裂症和自闭症。个体之间的互动是几个物种（包括斑马鱼）的一个重要方面和适应性反应。催产素是一种与社会行为相关的神经内分泌激素。本研究的目的是调查谷氨酸NMDA受体的非竞争性拮抗剂MK-801对斑马鱼社会互动和攻击行为的影响。我们还研究了催产素、催产素受体激动剂卡贝缩宫素和催产素受体拮抗剂L-368,899对这些影响的调节作用。我们的结果表明，MK-801导致在最靠近同种鱼群的区域停留的时间以及在最靠近镜像的区域停留的时间减少，这表明对社会行为有影响。在暴露于MK-801后用催产素治疗能够重新建立在最靠近同种鱼群的区域停留的时间以及在最靠近镜像的区域停留的时间。此外，为了支持催产素途径在调节这些反应中的作用，我们表明催产素受体激动剂卡贝缩宫素恢复了由MK-801诱导的社会和攻击行为缺陷。然而，催产素受体拮抗剂L-368,899不能逆转由MK-801诱导的行为变化。这项研究支持了NMDA受体和催产素能系统在调节社会行为和攻击行为中的关键作用，这可能与自闭症和精神分裂症相关的机制有关。
