Dehydrocorydaline induced antidepressant-like effect in a chronic unpredictable mild stress mouse model via inhibiting uptake-2 monoamine transporters

Abstract Dehydrocorydaline, is an active alkaloid compound in Corydalis yanhusuo W. T. Wang. We found dehydrocorydaline induced antidepressant-like effects in a chronic unpredictable mild stress mouse model, but the exact mechanisms have not been addressed. We speculated that dehydrocorydaline may have an antidepressant effect via inhibiting monoamine transporters in the brain. We evaluated the mechanism of action of dehydrocorydaline by examining the levels of monoamine transmitters (5-HT, NE and DA) in the prefrontal cortex in chronic unpredictable mild stress mice. Then, we used cell models and the mouse synaptosome to study molecular and cellular mechanisms underlying these behaviors and monoamine alterations by dehydrocorydaline. Our results indicated that dehydrocorydaline affects the concentrations of monoamine transmitters and decreases the turnover ratio, which indicates increased neuronal activity. The possible mechanism is that dehydrocorydaline potently inhibits uptake-2 transporters with the IC50 values of 0.1–4 μM and could inhibit the reuptake of 5-HT/DA/NE in the synaptosome. These data suggest that dehydrocorydaline has an antidepressant effect that is likely related to changing the content of monoamines in the brain by inhibiting uptake-2 transporters.