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拉莫三嗪治疗可逆转母爱剥夺成年大鼠的抑郁样行为,并改变其大脑中的脑源性神经营养因子水平。

Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats.

机构信息

Laboratório de Neurociências and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil.

出版信息

Pharmacol Biochem Behav. 2012 May;101(3):348-53. doi: 10.1016/j.pbb.2012.01.019. Epub 2012 Jan 27.

DOI:10.1016/j.pbb.2012.01.019
PMID:22306746
Abstract

Lamotrigine is an anticonvulsant and has an antiglutamatergic action, which may contribute to its antidepressant effects, since glutamate has been linked to depression. The purpose of the present study was to investigate the behavioral and molecular effects of lamotrigine treatment in maternally deprived rats. To this aim, deprived and non-deprived male rats were treated with lamotrigine (20 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed in the forced swimming and open field tests. In addition to this, the BDNF and NGF levels were assessed in the prefrontal cortex, hippocampus and amygdala. In the course of this study we demonstrated that maternally deprived rats treated with saline and lamotrigine showed an increase in their immobility time and a decrease in the climbing and swimming times when compared with non-deprived rats treated with saline alone. Treatment with lamotrigine reversed the increase in the immobility time in the deprived rats. The BDNF levels were decreased in the amygdala in deprived rats treated with saline, and treatment with lamotrigine reversed this decrease. The NGF levels were decreased in the hippocampus in deprived rats treated with saline, but treatment with lamotrigine did not reverse this decrease. In conclusion, lamotrigine showed antidepressant effects in the forced swimming test, and it presented positive effects on the BDNF protein levels in the amygdala of maternally deprived rats.

摘要

拉莫三嗪是一种抗惊厥药,具有抗谷氨酸作用,这可能有助于其抗抑郁作用,因为谷氨酸与抑郁症有关。本研究的目的是研究拉莫三嗪治疗在母爱剥夺大鼠中的行为和分子效应。为此,剥夺和非剥夺的雄性大鼠在成年期每天接受拉莫三嗪(20mg/kg)治疗 14 天。然后在强迫游泳和旷场试验中评估它们的行为。除此之外,还评估了前额叶皮层、海马体和杏仁核中的 BDNF 和 NGF 水平。在本研究过程中,我们证明与单独用生理盐水治疗的非剥夺大鼠相比,用生理盐水和拉莫三嗪治疗的母爱剥夺大鼠的不动时间增加,攀爬和游泳时间减少。拉莫三嗪治疗逆转了剥夺大鼠的不动时间增加。用生理盐水治疗的剥夺大鼠的杏仁核中的 BDNF 水平降低,而拉莫三嗪治疗则逆转了这种降低。用生理盐水治疗的剥夺大鼠的海马体中的 NGF 水平降低,但拉莫三嗪治疗没有逆转这种降低。总之,拉莫三嗪在强迫游泳试验中表现出抗抑郁作用,并且对母爱剥夺大鼠杏仁核中的 BDNF 蛋白水平有积极影响。

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