Obsessive-compulsive disorder (OCD) is a disabling disease characterized by distressing obsessions and repetitive compulsions. The etiology of OCD is poorly known, and mouse modeling allows to clarify the genetic and neurochemical basis of this disorder and to investigate potential treatments. This study evaluates the impact of the 5-HT1B agonist RU24969 on the induction of OCD-like behaviours in female BALB/c mice (), distributed across five groups receiving varying doses of RU24969. Behavioural assessments, including marble test, tail suspension test, sucrose preference test, forced swim test, and nestlet shredding test, were conducted. Gene expression and protein quantitation of Gabra1 and serotonin transporter in mouse brain were also performed. Marble-burying behaviour increased significantly at high doses of RU24969 (15-20 mg/kg). The forced swimming test consistently showed elevated values at the same high concentrations, compared to the control. Altered reward-seeking behaviour was indicated by the sucrose preference test, notably at 15 and 20 mg/kg doses of RU24969. Nestlet shredding results did not show statistical significance among the tested animal groups. Gene expression analysis revealed reduced Gabra1 expression with increasing doses of RU, while serotonin transporter was not related to varying doses of RU24969. Western blotting corroborated these trends. The results underscore complex interactions between the serotonin system, GABAergic signaling, and OCD-relevant behaviours and suggest the use of intraperitoneal injection of 15 mg/kg of RU24969 to induce OCD-like behaviour in BALB/c mouse models.

中文翻译：

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使用 RU24969 在 BALB/c 小鼠中建立强迫症模型：最佳剂量选择的分子和行为研究

强迫症（OCD）是一种致残性疾病，其特征是令人痛苦的强迫观念和重复性强迫行为。强迫症的病因尚不清楚，小鼠模型可以阐明这种疾病的遗传和神经化学基础，并研究潜在的治疗方法。本研究评估了 5-HT1B 激动剂 RU24969 对诱导雌性 BALB/c 小鼠强迫症样行为的影响（），分布在接受不同剂量 RU24969 的五组中。进行行为评估，包括弹珠测试、悬尾测试、蔗糖偏好测试、强迫游泳测试和燕窝撕碎测试。还进行了小鼠大脑中 Gabra1 和血清素转运蛋白的基因表达和蛋白质定量。高剂量 RU24969（15-20 毫克/千克）时，大理石埋藏行为显着增加。与对照相比，强迫游泳测试在相同高浓度下始终显示出升高的值。蔗糖偏好测试表明寻求奖励行为发生了改变，特别是在 15 和 20 mg/kg 剂量的 RU24969 下。雀巢粉碎结果在测试的动物组中没有显示出统计学显着性。基因表达分析显示，Gabra1 表达随着 RU 剂量的增加而降低，而血清素转运蛋白与不同剂量的 RU24969 无关。蛋白质印迹证实了这些趋势。结果强调了血清素系统、GABA能信号传导和强迫症相关行为之间复杂的相互作用，并建议使用腹腔注射 15 mg/kg RU24969 在 BALB/c 小鼠模型中诱导强迫症样行为。