This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)‐induced autism‐like symptoms. Pregnant rats received VPA (600 mg/kg/i.p.) once at 12.5 gestational days for autism‐like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n = 7). Offspring received prenatal PGB (15 & 30 mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15 + VPA, and PGB30 + VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism‐like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose‐dependent increase in pain threshold in prenatally VPA exposed rats in tail‐flick and hot plate test. Also, there was a sex‐related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB‐treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism‐like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism‐like symptoms in rat offspring.

中文翻译：

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产前普瑞巴林与丙戊酸诱导的后代大鼠自闭症的一些行为参数的性别依赖性改变有关

本研究旨在评估产前普瑞巴林 (PGB) 暴露对丙戊酸 (VPA) 诱导的自闭症样症状动物模型中大鼠后代行为变化的影响。妊娠大鼠在妊娠 12.5 天时接受一次 VPA (600 mg/kg/ip) 以诱导后代出现自闭症样症状。分娩后，每名母亲的单雄和单雌后代在成年第 60 天（n = 7）时随机选择进行行为测试（焦虑、疼痛反应、愉悦和运动功能）。后代在妊娠 9.5 至 15.5 天期间单独或与 VPA（PGB15、PGB30、PGB15 + VPA 和 PGB30 + VPA）联合接受产前 PGB（15 和 30 毫克/千克/腹腔注射）。对照后代在同一时期接受生理盐水。结果表明，产前 VPA 暴露与大鼠后代的自闭症样行为有关。妊娠期间的 PG​​B 治疗显示后代的高架十字迷宫和露天试验中蔗糖偏好测试和焦虑显着减少。此外，在甩尾和热板试验中，PGB 治疗在产前 VPA 暴露的大鼠中表现出剂量依赖性的疼痛阈值增加。此外，在横梁平衡和旷场试验中，运动功能存在与性别相关的显着损害，雄性大鼠比雌性大鼠受到的影响更大。然而，在产前 PGB 治疗的大鼠后代中没有观察到蔗糖偏好和疼痛敏感性的显着性别差异。总之，产前暴露于 VPA 增加了后代大鼠出现自闭症样行为的风险，