Differential Effects of Valproic Acid on Immobility Responses and Locomotor Activity in Female and Male Rats

Oscar Morales-Dionisio, F. Cruz, M. Franco-Colín, Oriana Hidalgo-Alegria, G. Flores, J. Luna-Muñoz, L. Garcés-Ramírez
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引用次数: 2

Abstract

Valproic acid (VPA) is used in the treatment of epilepsy and behavioral disorders. However, the exposure to VPA during pregnancy increases the risk of having offspring with autism spectrum disorder (ASD). Reports indicate that men are more likely to suffer ASD than women who were exposed to VPA prenatally. Few studies have related the sex differences and behavioral changes in the ASD rat model. Our aim was to determinate whether male and female Wistar rats whose mothers were exposed to either VPA (600 mg/kg; animal model for ASD) or saline (0.9%) i.p. at 12.5 day of gestation, have different effects on immobility induce by clamping (IC), dorsal immobility (DI), catalepsy, locomotor activity, stereotypes, and analgesia (tail flick). For this purpose, we made four groups (n = 8). Group: A) saline male rats, B) saline female rats, C) VPA male rats and D) VPA female rats. At 35 (prepubertal age), 56 (postpubertal age) and 180 days, we tested the behaviors previously mentioned. Finding that VPA has the same effect on IC, catalepsy, and analgesia in male and female rats, the time of these tests was increased. However, VPA only has an effect on DI in males but not in female rats. On the contrary, there is hyperactivity and an increase of stereotypes in female but not in male rats. Thereby, VPA has an effect on the three immobility responses tested (IC, DI and catalepsy), locomotor activity and analgesia but in a differential way on DI, stereotypes and locomotor activity between male and female rats.
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丙戊酸对雌雄大鼠静止反应和运动活动的不同影响
丙戊酸(VPA)用于治疗癫痫和行为障碍。然而,在怀孕期间接触VPA会增加后代患自闭症谱系障碍(ASD)的风险。报告显示,男性比产前接触VPA的女性更容易患ASD。很少有研究将ASD大鼠模型中的性别差异和行为改变联系起来。我们的目的是确定雄性和雌性Wistar大鼠的母亲是否暴露于VPA (600 mg/kg;ASD动物模型)或生理盐水(0.9%)在妊娠12.5天灌胃,对夹持(IC)、背侧不动(DI)、麻痹、运动活动、刻板印象和镇痛(甩尾)诱导的不动有不同的影响。为此,我们分为四组(n = 8): A)生理盐水雄性大鼠,B)生理盐水雌性大鼠,C) VPA雄性大鼠,D) VPA雌性大鼠。在35岁(青春期前),56岁(青春期后)和180天,我们测试了上述行为。发现VPA对雄性和雌性大鼠的IC、麻痹和镇痛作用相同,这些试验的时间增加。然而,VPA仅对雄性大鼠的DI有影响,而对雌性大鼠没有影响。相反,雌性大鼠有多动症和刻板印象的增加,而雄性大鼠没有。因此,VPA对测试的三种静止反应(IC、DI和catalepsy)、运动活动和镇痛有影响,但对雄性和雌性大鼠的DI、刻板印象和运动活动有不同的影响。
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