Activation of monoaminergic system contributes to the antidepressant- and anxiolytic-like effects of J147

Abstract

Major depressive disorder (MDD) is a severe mental disorder, which is closely related to the deficiency of monoamine neurotransmitters. Our previous study suggested that acute treatment with J147, a novel curcumin derivative, produced antidepressant-like effects in mouse model of depression by regulation of 5-HT receptor subtypes. However, it is still unknown whether the antidepressant-like effects of J147 are involved in activation of central monoaminergic system. In this study, a series of classical behavior tests were employed to assess the involvement of monoaminergic system in antidepressant- and anxiolytic-like effects after sub-acute treatment of mice with J147 for 3 days. The results suggested that J147 at 10 mg/kg significantly reduced the immobility time in both the tail suspension and forced swimming tests, but didn't show effects in the sucrose preference test. Similarly, sub-acute treatment of J147 did not induce amelioration in novelty suppressed feeding test. J147 increased duration and crossing time in the central area, but did not show significant change in rearing counts in the open field test. In neurochemical assays, studies suggested that serotonin and noradrenaline levels were significantly increased in the frontal cortex and hippocampus after treatment of J147 by the high-performance liquid chromatography (HPLC) with an electrochemical detector. Moreover, J147-induced significant inhibition of monoamine oxidase A activity. These findings suggest that the antidepressant- and anxiolytic-like effects of J147 might be related to the monoaminergic system by the evidence that high dose of J147 inhibits monoamine oxidase (MAO)-A activity and increases synaptic monoamines in the mouse brain.

Keywords: Anxiety; Depression; J147; Monoamine; Monoamine oxidase.