Department of Biological Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon.
Department of Agriculture, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut, Lebanon.
Behav Neurol. 2024 Mar 25;2024:4504858. doi: 10.1155/2024/4504858. eCollection 2024.
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 ( = 30), 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.
强迫症（OCD）是一种使人丧失能力的疾病，其特征是令人痛苦的强迫观念和重复的强迫行为。OCD 的病因知之甚少，而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 BALB/c 雌性小鼠（n=30）产生 OCD 样行为的影响，这些小鼠分为五组，接受不同剂量的 RU24969。进行了行为评估，包括 Marble 试验、悬尾试验、蔗糖偏好试验、强迫游泳试验和巢丝撕碎试验。还对小鼠大脑中的 Gabra1 和血清素转运蛋白的基因表达和蛋白定量进行了分析。在 RU24969 的高剂量（15-20mg/kg）下，埋 Marble 行为显著增加。与对照组相比，在相同的高浓度下，强迫游泳试验始终显示出较高的值。蔗糖偏好试验表明，奖赏寻求行为发生改变，特别是在 RU24969 的 15 和 20mg/kg 剂量下。巢丝撕碎试验结果在受试动物组之间没有显示出统计学意义。基因表达分析显示，随着 RU 剂量的增加，Gabra1 的表达减少，而血清素转运体与 RU24969 的不同剂量无关。Western blot 验证了这些趋势。结果强调了血清素系统、GABA 能信号与 OCD 相关行为之间的复杂相互作用，并表明腹腔注射 15mg/kg 的 RU24969 可用于诱导 BALB/c 小鼠模型产生 OCD 样行为。
