【摘要】 目的研究胡椒碱及其衍生物3,4次甲二氧桂皮酰哌啶的抗抑郁作用,并对其作用机理进行初步探讨。方法利用小鼠强制游泳实验、悬尾实验等考察胡椒碱和3,4次甲二氧桂皮酰哌啶的抗抑郁作用,并通过测定不同脑区内单胺类神经递质质量浓度以及全脑单胺氧化酶活性变化,探讨作用机制。结果胡椒碱和3,4次甲二氧桂皮酰哌啶(10、20 mg.kg-1)长期给药后,能明显缩短小鼠在行为学实验中的不动状态时间,并且该作用随剂量增大效应逐渐降低,高剂量(80 mg.kg-1)表现出明显的中枢神经抑制作用;能显著提高脑内5羟色胺水平,而对脑内肾上腺素递质水平未见明显影响;具有较弱的单胺氧化酶抑制作用。结论胡椒碱和3,4次甲二氧桂皮酰哌啶具有较好的抗抑郁作用,其作用是通过上调中枢神经系统5羟色胺或多巴胺水平实现的。更多还原

【Abstract】 Objective To investigate antidepressant-like effects and mechanisms of piperine and its derivative,3,4-methylene dioxy cinnamoyl piperidine（MDP）.Methods The behavioral studies were performed in two depressive models:forced swimming test（FST）and tail suspension test（TST）.To further explore the mechanisms underlying their antidepressant-like activities,the brain monoamine levels and monoamine oxidase activities were also determined.Results The research results indicated that after two weeks of chronic administration,piperine and MDP(10-20 mg·kg^-1)could significantly reduce the duration of immobility in both FST and TST without accompanying changes in locomotor activity in the open-field test.But at the dose of 80 mg·kg^-1,the antidepressant activities of both piperine and MDP returned to the control levels in the TST and FST.In the monoamine assay,chronic MDP administration significantly elevated the dopamine levels in striatum,hypothalamus and hippocampus,and also increased the serotonin levels in the hypothalamus and hippocampus.In contrast,chronic treatment of piperine only enhanced the serotonin levels in the hypothalamus and hippocampus but did not influence the dopamine level.Moreover,both piperine and MDP showed no effects on the levels of noradrenaline in these brain regions.The MAO activity assay also indicated that piperine and MDP showed a minor MAO inhibitory activity.Conclusions In the present study,we demonstrated that the antidepressant-like effects of piperine and MDP might be dependent on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake.Antidepressant properties of piperine are supposed to be mediated via the up-regulation of serotonergic system,whereas the mechanisms of antidepressant action of MDP might due to its dual up-regulation of both serotonergic and dopaminergic systems.更多还原