R-Baclofen Treatment Corrects Autistic-like Behavioral Deficits in the RjIbm(m):FH Fawn-Hooded Rat Strain

Pharmaceuticals Pub Date : 2024-07-13 DOI:10.3390/ph17070939
Anita Varga, R. Kedves, Katalin Sághy, Dénes Garab, Ferenc Zádor, Balázs Lendvai, György Lévay, Viktor Román
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Abstract

The Fawn-hooded rat has long been used as a model for various peripheral and central disorders and the data available indicate that the social behavior of this strain may be compromised. However, a thorough description of the Fawn-hooded rat is unavailable in this regard. The objective of the present study was to investigate various aspects of the Fawn-hooded rat’s social behavior in depth. Our results show that several facets of socio-communicational behavior are impaired in the RjIbm(m):FH strain, including defective ultrasonic vocalizations in pups upon maternal deprivation, reduced social play in adolescence and impaired social novelty discrimination in adulthood. In addition, Fawn-hooded rats exhibited heightened tactile sensitivity and hyperactivity. The defects observed were comparable to those induced by prenatal valproate exposure, a widely utilized model of autism spectrum disorder. Further on, the pro-social drug R-baclofen (0.25–1 mg/kg) reversed the autistic-like defects observed in Fawn-hooded rats, specifically the deficiency in ultrasonic vocalization, tactile sensitivity and social novelty discrimination endpoints. In conclusion, the asocial, hypersensitive and hyperactive phenotype as well as the responsivity to R-baclofen indicate this variant of the Fawn-hooded rat strain may serve as a model of autism spectrum disorder and could be useful in the identification of novel drug candidates.
R-巴氯芬治疗可纠正RjIbm(m):FH小黄冠大鼠品系的自闭症样行为缺陷
长期以来,黄褐大鼠一直被用作各种外周和中枢疾病的模型,现有数据表明,该品系大鼠的社交行为可能会受到影响。然而,在这方面还没有关于黄盖大鼠的详尽描述。本研究的目的是深入研究黄盖大鼠社会行为的各个方面。研究结果表明,RjIbm(m):FH品系大鼠社会交往行为的多个方面都受到了损害,包括幼鼠在被剥夺母性后的超声波发声缺陷、青春期社会游戏减少以及成年期社会新奇事物辨别能力受损。此外,黄褐大鼠还表现出更高的触觉敏感性和多动性。观察到的缺陷与产前接触丙戊酸钠诱发的缺陷相当,丙戊酸钠是一种广泛使用的自闭症谱系障碍模型。此外,亲社会药物 R-巴氯芬(0.25-1 毫克/千克)可逆转在小鹿戴帽大鼠身上观察到的类似自闭症的缺陷,特别是超声波发声、触觉敏感性和社会新奇辨别终点的缺陷。总之,自闭症大鼠的非社会性、高敏感性和多动表型以及对R-巴氯芬的反应性表明,这种变异的小鹿帽大鼠品系可作为自闭症谱系障碍的模型,并可用于鉴定新型候选药物。
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