2-B-P-021 〇出山 諭司^1,2、青木 駿¹、杉江 莉奈子²、金田 勝幸^1,2 Satoshi Deyama^1,2, Shun Aoki¹, Rinako Sugie², Katsuyuki Kaneda^{1,2 1}金沢大・院薬・薬理、²金沢大・薬・薬理 ¹Lab. Mol. Pharmacol., Inst. Med., Pharmaceut., Health Sci., Kanazawa Univ., ²Lab. Mol. Pharmacol., Sch. Pharmaceut. Sci., Kanazawa Univ. Previous studies demonstrated that the extract of the fruit of Citrus aurantium (bitter orange) produces antidepressant-like and anxiolytic-like effects. However, it is unclear which constituents of C. aurantium are involved in these beneficial effects. Here, we examined the antidepressant-like effects of neohesperidin (NH), a flavanone glycoside found in C. aurantium, in naïve and repeated prednisolone (PSL)-induced depression model mice. We found that oral (p.o.) administration of NH (5 and 50 mg/kg) dose-dependently produced antidepressant-like effect in naïve mice in the forced swim test (FST) 1 h after the treatment without affecting locomotor activity and anxiety-like behavior in the open field test (OFT). However, NH failed to produce antidepressant-like effect in the FST 24 h after the treatment. We also examined the effect of NH (50 mg/kg, p.o.) on depression-like behavior induced by repeated subcutaneous injections of PSL (50 mg/kg, once a day for 5–6 days). Repeated PSL injections significantly increased immobility in the FST, which was not reversed by acute intraperitoneal injection of desipramine (30 mg/kg). In contrast, a single dose of NH (50 mg/kg, p.o.) blocked repeated PSL-induced depression-like behavior in the FST 24 h after the treatment, which was blocked by intra-medial prefrontal cortex (mPFC) infusion of rapamycin (0.01 nmol/side), a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor. These results suggest that NH produces antidepressant-like effect via mTORC1 activation in the mPFC.