Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
Behav Brain Res. 2022 Feb 10;418:113676. doi: 10.1016/j.bbr.2021.113676. Epub 2021 Nov 18.
Resolvin E1 (RvE1) is an anti-inflammatory lipid mediator derived from eicosapentaenoic acid. We previously demonstrated that intracerebroventricular (i.c.v.) and intra-medial prefrontal cortex (mPFC) infusions of RvE1 produce antidepressant-like effects in a lipopolysaccharide-induced depression mouse model. To further confirm the antidepressant-like effect of RvE1, the present study examined whether RvE1 ameliorated depression-like behavior induced by repeated injections of prednisolone (PSL), a synthetic glucocorticoid, in male ICR mice. We first ascertained whether repeated subcutaneous treatment with PSL (50 mg/kg, once a day) affected locomotor activity and anxiety-like behavior in the open field test (OFT; after a 5-day PSL treatment) and induced depression-like behavior in the tail suspension test (TST; after a 6-day PSL treatment) and forced swim test (FST; after a 7-day PSL treatment). Repeated PSL injections significantly increased immobility in the FST, which was not ameliorated by acute desipramine treatment (30 mg/kg, i.p.), but not in the TST, without affecting locomotor activity and anxiety-like behavior in the OFT. Subsequently, we investigated the therapeutic effects of i.c.v. (1 ng) and intra-mPFC (50 pg/side) infusions of RvE1 in the repeated PSL-induced depression mouse model using the OFT and FST after 5- and 6-day PSL treatments, respectively. The repeated PSL-induced increase in immobility in the FST was significantly attenuated by both i.c.v. and intra-mPFC infusions of RvE1 without affecting the locomotor activity and anxiety-like behavior. In addition, a single i.c.v. infusion of RvE1 immediately before the first or fourth injection of PSL also attenuated PSL-induced depression-like behavior in the FST, suggesting the preventive effect of RvE1. These results indicate that RvE1 produces antidepressant-like effects in a mouse model of repeated PSL-induced depression.
解析 E1（RvE1）是一种源自二十碳五烯酸的抗炎脂质介质。我们之前的研究表明，脑室（i.c.v.）和内侧前额叶皮层（mPFC）内注射 RvE1 可在脂多糖诱导的抑郁小鼠模型中产生抗抑郁样作用。为了进一步证实 RvE1 的抗抑郁样作用，本研究检查了 RvE1 是否改善了反复注射合成糖皮质激素地塞米松（PSL）诱导的雄性 ICR 小鼠的抑郁样行为。我们首先确定了重复皮下给予 PSL（50mg/kg，每天一次）是否会影响旷场试验（OFT；在 5 天 PSL 治疗后）中的运动活动和焦虑样行为，并诱导在悬尾试验（TST；在 6 天 PSL 治疗后）和强迫游泳试验（FST；在 7 天 PSL 治疗后）中诱导抑郁样行为。重复 PSL 注射显著增加了 FST 中的不动性，而急性去甲丙咪嗪治疗（30mg/kg，ip）并未改善，而在 TST 中则没有改善，而不影响 OFT 中的运动活动和焦虑样行为。随后，我们在分别用 5 天和 6 天 PSL 治疗后进行的 OFT 和 FST 中，研究了脑室（1ng）和内侧前额叶皮层（50pg/侧）内注射 RvE1 在重复 PSL 诱导的抑郁小鼠模型中的治疗效果。重复 PSL 诱导的 FST 中不动性的增加被脑室和内侧前额叶皮层内注射 RvE1 明显减弱，而不影响运动活动和焦虑样行为。此外，在第一次或第四次 PSL 注射前，单次脑室注射 RvE1 也可减轻 PSL 诱导的 FST 中抑郁样行为，提示 RvE1 具有预防作用。这些结果表明，RvE1 在重复 PSL 诱导的抑郁小鼠模型中产生抗抑郁样作用。
