Venlafaxine treatment stimulates expression of brain-derived neurotrophic factor protein in frontal cortex and inhibits long-term potentiation in hippocampus

Antidepressant action may involve stimulation of brain-derived neurotrophic factor (BDNF). BDNF also regulates long-term potentiation (LTP). We hypothesized that the 5-HT and norepinephrine reuptake inhibitor, venlafaxine, would stimulate BDNF expression and alter LTP more effectively than the selective 5-HT reuptake inhibitor, citalopram. To test this, we administered venlafaxine or citalopram to rats for 1 or 3 weeks; control rats received vehicle only. We measured BDNF protein in hippocampal and frontal cortex homogenates, and serum. We assessed LTP in area cornu ammonis region 1 (CA1) of in vitro hippocampal brain slices. We also examined input/output function to determine if basal synaptic transmission in area CA1 was altered. Compared to vehicle control, frontal cortex BDNF protein was significantly greater after three, but not one, weeks of venlafaxine treatment. In contrast, citalopram (1 or 3 weeks) did not stimulate BDNF. The stimulatory effect of venlafaxine treatment on BDNF was superimposed on a general time-dependent decrease in expression which was seen in both vehicle control and citalopram-treated animals. LTP was significantly impaired in slices from venlafaxine-treated rats after both 1 and 3 weeks of treatment, but LTP appeared normal in slices from citalopram-treated and vehicle control rats. The LTP impairment caused by venlafaxine treatment was independent of changes in BDNF: LTP was impaired after only 1 week of treatment, prior to any effect on BDNF, and LTP magnitude was not correlated with BDNF protein concentration. Input/output function was significantly but equally reduced after 3 weeks of citalopram, venlafaxine, or control treatment. Decreased BDNF protein in citalopram and vehicle control animals, and decreased input/output function may be consequences of individual housing of animals, which we used to ensure proper dosing. Venlafaxine stimulation of BDNF and inhibition of LTP may be related to the reported effectiveness of venlafaxine in treatment of depression.     

Serotonin transporter gene polymorphisms and treatment-resistant depression

Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.     

积雪草总三萜酸及其主要成分的抗抑郁活性研究

目的:探讨积雪草总三萜酸和其主要成分积雪草酸、羟基积雪草酸的抗抑郁作用.方法:采用小鼠强迫游泳实验、小鼠悬尾实验、开野实验和拮抗利血平所致的小鼠眼睑下垂实验,分别以小鼠不动时间、自主活动数和拮抗率作为评价指标.结果:在强迫游泳实验中积雪草总三萜酸、积雪草酸、羟基积雪草酸60 mg/kg、120 mg/kg剂量均能显著缩短小鼠不动时间,在悬尾实验中30 mg/kg、60 mg/kg、120 mg/kg剂量均能显著缩短小鼠不动时间,开野实验结果表明给药后小鼠的自主活动无明显变化,在利血平拮抗实验中积雪草总三萜酸、积雪草酸、羟基积雪草酸均可减少小鼠眼睑下垂.结论:积雪草总三萜酸、积雪草酸、羟基积雪草酸有抗抑郁作用.     

我院门诊抗抑郁药物的使用现状及趋势分析

目的了解门诊抗抑郁药物的使用现状及发展趋势。方法对2004～2006年中国人民解放军总医院门诊抗抑郁药物用药金额、用药频度（DDDs）及日均费用等进行统计，并对2006年6月份来门诊诊疗的抑郁症患者的处方进行整理并分析。结果2005年门诊抗抑郁药的销售金额与DDDs比2004年分别增长了148．8％和103、3％，2006年比2005年的均有所下降。连续两年增幅较大的是西酞普兰和舍曲林。结论门诊抗抑郁药的使用量呈逐年上升趋势，其中选择性5-羟色胺再摄取抑制剂氟西汀、帕罗西汀等在门诊治疗抑郁症中起着举足轻重的作用。     

香砂六君子汤的抗抑郁活性部位筛选

目的：筛选香砂六君子汤的抗抑郁活性部位.方法：选用小鼠行为绝望模型（小鼠强迫游泳实验）评价抗抑郁作用;用荧光分光光度法测定单胺类神经递质.结果：香砂六君子汤的5个提取部位均可不同程度地降低小鼠的不动时间,其中正丁醇部位的作用最强;各部位第2周效果比第1周强.正丁醇部位,乙醇中、高剂量部位和水高剂量部位均显著提高了5-HT、NA和DA在海马、纹状体两个脑区中的含量;其中正丁醇部位对提高海马内3种神经递质含量的作用最强,乙醇高剂量部位对提高纹状体内3种神经递质含量的作用最强.结论：香砂六君子汤5个提取部位具有不同程度的抗抑郁活性,其活性成分主要分布在正丁醇和乙醇高剂量部位,可能是通过多方面影响单胺类神经递质系统来达到抗抑郁的目的.     

抗抑郁药米氮平的新合成方法

目的：合成抗抑郁药米氮平。方法：以N-甲基乙醇胺、氧化苯乙烯和2-氨基烟酸为原料，经亲核开环、氯代、碱化、还原、胺烷基化和环合6步制得了抗抑郁药米氮平。结果：文献报道的相应各步反应条件得以优化，产率由22．6％提高到49．5％，各中间体及产物经红外光谱、核磁共振氢谱确证。结论：本方法简化了操作步骤，优化了反应条件，降低了成本，提高了收率。     

血脑屏障上的P-糖蛋白与精神类药物

P-糖蛋白(P-gp)是ABC超家族的重要成员,而许多精神药物包括抗精神分裂症药物和抗抑郁症药物,都是P-gp的底物。本文对近年来国内外有关P-gp对精神药物限制进入血脑屏障的相关研究,进行了综述。     

郁金抗抑郁作用的实验研究

目的观察郁金对小鼠抑郁的影响。方法采用小鼠强迫游泳实验、悬尾实验和拮抗利血平所致的抑郁症状实验。结果郁金高、中、低剂量组均可缩短小鼠强迫游泳、悬尾不动时间和拮抗利血平所致小鼠体温下降作用(P<0.01,P<0.05),郁金高、中剂量组可拮抗利血平所致小鼠运动不能作用(P<0.01),郁金高剂量组拮抗利血平所致小鼠眼睑下垂作用(P<0.05)。结论郁金对小鼠抑郁症的强迫游泳模型、悬尾模型和拮抗利血平所致的抑郁症模型均有治疗作用,且该作用与药物的剂量密切相关。