Jornada Luciano K, Moretti Morgana, Valvassori Samira S, Ferreira Camila L, Padilha Peterson T, Arent Camila O, Fries Gabriel R, Kapczinski Flavio, Quevedo João
Laboratory of Neurosciences and National Science and Technology Institute for Translational Medicine, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88808-000 Criciúma, SC, Brazil.
J Psychiatr Res. 2010 Jun;44(8):506-10. doi: 10.1016/j.jpsychires.2009.11.002. Epub 2009 Dec 1.
There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
有大量证据表明脑源性神经营养因子（BDNF）参与双相情感障碍（BD）的发病机制。向脑室内（ICV）注射哇巴因（OUA），一种特异性钠钾ATP酶抑制剂，可诱导大鼠活动过度，已被用作躁狂症的动物模型。本研究旨在探讨锂盐（Li）和丙戊酸盐（VPT）在哇巴因诱导的躁狂症动物模型中的作用。在逆转模型中，动物接受单次ICV注射OUA或脑脊液（aCSF）。从ICV注射后的第二天起，大鼠每天接受两次腹腔内（IP）注射生理盐水（SAL）、Li或VPT，持续6天。在维持治疗（预防模型）中，大鼠每天接受两次IP注射Li、VPT或SAL，持续12天。在治疗的第7天，动物接受单次ICV注射OUA或aCSF。ICV注射后，情绪稳定剂的治疗继续进行6天。使用旷场试验测量运动活动，并通过夹心ELISA法测量大鼠海马和杏仁核中的BDNF水平。在两个实验中，Li和VPT均在旷场试验中逆转了与OUA相关的多动行为。在第一个和第二个实验中，OUA降低了海马和杏仁核中的BDNF水平，Li治疗可逆转并预防OUA给药后这些脑区BDNF表达的受损，但VPT不能。我们的结果表明，作为躁狂症的动物模型，本模型具有足够的表面效度、结构效度和预测效度。
