California State University, San Bernardino, Department of Psychology, 5500 University Parkway, San Bernardino, CA 92407, USA.
Behav Brain Res. 2022 Jun 3;427:113865. doi: 10.1016/j.bbr.2022.113865. Epub 2022 Mar 30.
Pharmacological activation of the serotonin (5-HT) 1B and 5-HT1A receptors has been shown to induce OCD-like perseverative circling and locomotor stereotypy in rodents. Although, several studies have examined how activation of these receptors facilitates these motor-associated OCD-like behaviors, it is not known how acute 5-HT1B and 5-HT1A activation impacts behavioral inflexibility, a common trait related to OCD. The current study examined how acute 5-HT1B/1A receptor agonist RU24969 treatment at 0.01, 0.1, and 1.0 mg/kg impacted behavioral flexibility in both female and male C57BL/6J mice. Behavioral flexibility was tested using a spatial reversal learning task, with probabilistic reward contingencies. In addition, locomotor activity and anxiety-like behaviors were also measured. RU24969 at 0.1 and 1.0 mg/kg impaired behavioral flexibility in both female and male C57BL/6J mice. RU24969 treatment at 1.0 mg/kg reduced locomotor activity in male mice, although RU24969 treatment did not significantly reduce locomotor activity in female mice. In the open field, 1.0 mg/kg elevated anxiety-like behavior in male mice only. Overall, these results demonstrate that acute 5-HT1B and 5-HT1A receptor activation leads to impairments in behavioral flexibility, a common trait associated with OCD.
5-羟色胺（5-HT）1B 和 5-HT1A 受体的药理学激活已被证明可诱导啮齿动物出现强迫症样持续转圈和运动刻板行为。尽管有几项研究检查了这些受体的激活如何促进这些与强迫症相关的运动行为，但目前尚不清楚急性 5-HT1B 和 5-HT1A 激活如何影响行为灵活性，这是与强迫症相关的常见特征。本研究检查了急性 5-HT1B/1A 受体激动剂 RU24969 在 0.01、0.1 和 1.0 mg/kg 剂量下如何影响雌性和雄性 C57BL/6J 小鼠的行为灵活性。使用具有概率奖励关联的空间反转学习任务测试行为灵活性。此外，还测量了运动活动和焦虑样行为。RU24969 在 0.1 和 1.0 mg/kg 剂量下损害了雌性和雄性 C57BL/6J 小鼠的行为灵活性。RU24969 治疗 1.0 mg/kg 减少了雄性小鼠的运动活动，尽管 RU24969 治疗并未显著减少雌性小鼠的运动活动。在开阔场中，仅 1.0 mg/kg 增加了雄性小鼠的焦虑样行为。总体而言，这些结果表明，急性 5-HT1B 和 5-HT1A 受体激活导致行为灵活性受损，这是与强迫症相关的常见特征。
