ABSTRACT
OBJECTIVE To study the antidepressant effects of ammoxetine(AMX)and the underlying mechanisms. METHODS Two behavioral despair models,the tail suspension test (TST) and the forced swimming test(FST),were used to evaluate the antidepressant-like effects of AMX 2.5-20 mg · kg-1 following oral administration. Monoamine neurotransmitter p-chloro-phenylalanine(p-CPA)andα-methyl-p-tyrosine(AMPT) depletion models in mice were used to investigate the effects of AMX on levels of 5-serotomin(5-HT)and norepinephrine(NE)in the brain. RESULLTS The results of behavioral study showed that compared with normal control group,AMX(10 and 20 mg · kg-1)reduced the immobility time of mice by 51.4% and 80.7% in the TST(P<0.05,P<0.01) or by 48.0% and 66.2% in the FST (P<0.05),respectively. Locomotion activity test indicated that AMX did not increase or decrease the movement distance of mice,demonstrating that AMX had no excitatory or inhibitory actions on the central nervous system. Moreover,AMX(5,10 and 20 mg·kg-1)exerted antidepressant effects in the p-CPA induced 5-HT depletion model and AMPT induced NE depletion model,as evidenced by the significantly reduced immobility time,ie,63.9%,93.4%,90.5% and 61.9%,77.2%,100% reduction in the TST (P<0.01),respectively,and AMX at the dose of 20 mg·kg-1 significantly increased the concentrations of 5-HT and NE by 144.7% and 57.2% in the mouse brain(P<0.05) ,respectively. CONCLUSION AMX has strong antidepressant-like effects in behavioral despair models and monoamine neurotransmitter depletion models in mice,which is involved in the increased levels of 5-HT and NE in the brain.