Involvement of adrenoceptors, dopamine receptors and AMPA receptors in antidepressant-like action of 7-O-ethylfangchinoline in mice.

Aim: 7-O-ethylfangchinoline (YH-200) is a bisbenzylisoquinoline derivative. The aim of this study was to investigate the antidepressant-like action and underlying mechanisms of YH-200 in mice.

Methods: Mice were treated with YH-200 (15, 30, and 60 mg/kg, ig) or tetrandrine (30 and 60 mg/kg, ig) before conducting forced swimming test (FST), tail suspension test (TST), or open field test (OFT).

Results: YH-200 (60 mg/kg) significantly decreased the immobility time in both FST and TST, and prolonged the latency to immobility in FST. YH-200 (60 mg/kg) was more potent than the natural bisbenzylisoquinoline alkaloid tetrandrine (60 mg/kg) in FST. Pretreatment with α1-adrenoceptor antagonist prazosin (1 mg/kg), β-adrenoceptor antagonist propranolol (2 mg/kg), dopamine D1/D5 receptor antagonist SCH23390 (0.05 mg/kg), dopamine D2/D3 receptor antagonist haloperidol (0.2 mg/kg) or AMPA receptor antagonist NBQX (10 mg/kg) prevented the antidepressant-like action of YH-200 (60 mg/kg) in FST. In contrast, pretreatment with α2 adrenoceptor antagonist yohimbine (1 mg/kg) augmented the antidepressant-like action of YH-200 (30 mg/kg) in FST. Chronic administration of YH-200 (30 and 60 mg/kg for 14 d) did not produce drug tolerance; instead its antidepressant-like action was strengthened. Chronic administration of YH-200 did not affect the body weight of mice compared to control mice.

Conclusion: YH-200 exerts its antidepressant-like action in mice via acting at multi-targets, including α1, α2 and β-adrenoceptors, D1/D5 and D2 /D3 receptors, as well as AMPA receptors.