Arzuaga Anna L, Teneqexhi Pamela, Amodeo Katelyn, Larson John R, Ragozzino Michael E
Department of Biological Sciences, University of Illinois Chicago, Chicago, IL 60607, USA.
Department of Psychology, University of Illinois Chicago, Chicago, IL 60607, USA.
Physiol Behav. 2025 Jun 1;295:114891. doi: 10.1016/j.physbeh.2025.114891. Epub 2025 Mar 29.
Autism spectrum disorder (ASD) is characterized by significant heterogeneity in the variety and severity of symptoms. Prenatal stress and/or exposure to antidepressants may be major contributors to ASD heterogeneity. To date, the effects of prenatal stress or selective serotonin reuptake inhibitor exposure have been primarily examined in common laboratory rat and mouse strains as opposed to in rodent models of autism. The present experiments determined in the BTBR mouse model of autism whether restraint stress (30 min session every 2 days during G4 - G18) and/or exposure to the SSRI, fluoxetine (3 mg/kg during G8 - G18) affects repetitive motor behaviors, anxiety and/or behavioral flexibility in offspring at adulthood. Male and female BTBR mice exhibited elevated grooming behavior compared to that of C57BL/6 J (B6) mice. The prenatal manipulations did not affect grooming in male BTBR mice, but the combination increased rearing and jumping. Prenatal stress, fluoxetine and the combination significantly reduced self-grooming, while concomitantly increasing locomotion in female BTBR mice. These prenatal manipulations also increased rearing and jumping behavior in female BTBR mice. In B6 mice, the prenatal stress conditions increased grooming behavior. In addition, male BTBR mice exposed to prenatal stress and fluoxetine along with female BTBR mice prenatally exposed to fluoxetine were impaired on reversal learning. The prenatal manipulations had no effect on anxiety in either mouse strain. The pattern of results suggest that prenatal exposure to stress and/or a SSRI have long-term effects on autism-like behaviors and may contribute to the heterogeneity and co-morbidity observed in autism.
自闭症谱系障碍（ASD）的特征是症状的种类和严重程度存在显著异质性。产前应激和/或接触抗抑郁药可能是导致ASD异质性的主要因素。迄今为止，产前应激或选择性5-羟色胺再摄取抑制剂暴露的影响主要在常见的实验大鼠和小鼠品系中进行了研究，而非在自闭症啮齿动物模型中。本实验在自闭症BTBR小鼠模型中确定了束缚应激（在G4 - G18期间每2天进行一次30分钟的实验）和/或接触选择性5-羟色胺再摄取抑制剂氟西汀（在G8 - G18期间为3毫克/千克）是否会影响成年后代的重复运动行为、焦虑和/或行为灵活性。与C57BL/6 J（B6）小鼠相比，雄性和雌性BTBR小鼠的理毛行为有所增加。产前干预对雄性BTBR小鼠的理毛行为没有影响，但两者结合会增加竖毛和跳跃行为。产前应激、氟西汀及其组合显著减少了雌性BTBR小鼠的自我理毛行为，同时增加了其运动能力。这些产前干预还增加了雌性BTBR小鼠的竖毛和跳跃行为。在B6小鼠中，产前应激条件增加了理毛行为。此外，产前暴露于应激和氟西汀的雄性BTBR小鼠以及产前暴露于氟西汀的雌性BTBR小鼠在逆向学习方面存在缺陷。产前干预对两种小鼠品系的焦虑均无影响。结果模式表明，产前暴露于应激和/或选择性5-羟色胺再摄取抑制剂对自闭症样行为有长期影响，可能导致自闭症中观察到的异质性和共病现象。
