Pharmacokinetic-pharmacodynamic Modeling of Monoamine Oxidase A Inhibitory Activity and Behavior Improvement by Curcumin in the Mouse Forced Swimming Test

Abstract

Aim To characterize the pharmacokinetic, pharmacodynamic and efficacy profiles of curcumin in animal model of depression. Methods The forced swimming test (FST) in mice was used in this study. The single and repeated (hourly for three times) oral administration of 2.5, 5 and 10 mg·kg −1 curcumin was performed in the FST. Brain monoamine oxidase A (MAO-A) in vitro and in vivo as well as behaviors were determined. The plasma curcumin concentration was analyzed using high performance liquid chromatography (HPLC) method. The pharmacokinetics of curcumin was described by a two-compartment pharmacokinetic model with a lag time in the mouse FST. Results The peak plasma concentration was observed at 0.75 h (single) and 2.75–3 h (repeated) after oral curcumin administration, and the plasma concentration was around detection limit at 6 h (single) and 14 h (repeated), respectively. Curcumin at nanogram concentrations showed monoamine oxidase A (MAO-A) inhibitory activity and behavioral improvement in the mouse FST. The maximum behavioral effects of climbing, swimming and immobility were achieved at 1–2 h (single) and 3–4 h (repeated), which paralleled that of the maximum MAO-A inhibitory effects in frontal cortex and hippocampus after oral curcumin administration in the mouse FST, respectively. Conclusion These results suggest that curcumin may indirectly produce behavioral improvement, and its antidepressant potency may not be dependent on its plasma concentration.