Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Laboratório de Sinalização Neural e Psicofarmacologia, Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Brain Res Bull. 2017 Sep;134:228-235. doi: 10.1016/j.brainresbull.2017.08.006. Epub 2017 Aug 9.
Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats.
锂（Li）是一种用于治疗双相情感障碍（BD）的情绪稳定剂。最近，临床前研究表明他莫昔芬（TMX）在治疗 BD 急性发作方面具有潜力。然而，TMX 用于治疗情绪障碍的长期使用存在争议。在这项研究中，我们评估了 TMX 或 Li 对雄性和雌性大鼠的认知行为以及大脑神经营养因子水平的影响。雄性和雌性 Wistar 大鼠通过灌胃接受水（对照组）、TMX 或 Li 治疗 28 天；然后对大鼠进行旷场试验（评估自发运动）和新物体识别和跳下抑制性回避试验（评估认知）。评估了受试大鼠海马体和额叶皮质中 NGF、BDNF 和 GDNF 的水平。给药后，雄性或雌性大鼠在旷场和抑制性回避试验中均未观察到明显差异。TMX 给药而非 Li 给药降低了雄性和雌性大鼠物体识别试验的识别指数。TMX 的慢性给药降低了，而 Li 增加了雄性和雌性大鼠海马体中 BDNF 的水平。TMX 降低了雌性大鼠海马体中 NGF 的水平。总之，可以认为 TMX 的长期治疗会通过降低大鼠大脑中神经营养因子的水平导致明显的认知障碍。
