DS-1226对慢性睡眠干扰所致小鼠抑郁行为的改善作用

目的研究人参皂苷水解产物DS-1226对慢性睡眠干扰小鼠的抗抑郁作用,为抗抑郁药物的研发提供科学依据。方法将72只雄性ICR小鼠分为空白对照组、模型组、阳性对照组(盐酸帕罗西汀,10 mg/kg)、DS-1226低剂量组(20 mg/kg)、中剂量组(40 mg/kg)、高剂量组(80 mg/kg)。除空白组外,其他组小鼠先进行3 d的滚筒适应,然后连续进行14 d睡眠干扰。采用体重监测、自主活动实验、悬尾实验、强迫游泳实验等实验方法,评价DS-1226的抗抑郁作用。结果连续进行14 d睡眠干扰后,与空白对照组相比,模型组体重显著下降,悬尾和强迫游泳不动时间显著增长。与模型组相比,DS-1226中剂量组显著逆转睡眠干扰所致的体重下降,其他各给药组均未能显著逆转睡眠干扰所致的体重下降;阳性药组的悬尾不动时间极显著减少,强迫游泳不动时间有减少趋势;DS-1226中剂量悬尾不动时间显著减少,强迫游泳不动时间有明显减少趋势;DS-1226高剂量组悬尾和强迫游泳不动时间均显著减少。结论 DS-1226具有改善慢性睡眠干扰小鼠抑郁样行为的作用。     

不同品系小鼠在三种常见抑郁检测方法中的行为学表现

目的探讨4种不同品系小鼠在3种实验（空场实验、悬尾实验及强迫游泳实验）中的行为学差异,为抗抑郁新药研究中的实验动物选择提供参考。方法利用空场实验检测C57BL/6、BALB/c、ICR、和昆明小鼠的自主活动能力和对新奇环境的探索能力;利用悬尾实验和强迫游泳实验检测它们在应激刺激下的行为绝望状态。结果在空场实验中,BALB/c、ICR和昆明小鼠的运动总路程、运动速度和运动时间明显高于C57BL/6小鼠（P〈0.05）,ICR和昆明小鼠的直立次数也明显高于C57BL/6小鼠（P〈0.05）;悬尾实验C57BL/6小鼠的不动时间显著长于其他3种品系小鼠（P〈0.05）,但是4种品系小鼠在强迫游泳实验中的不动时间差异无显著性。结论 C57BL/6小鼠自发活动量低,对新奇环境的探索能力差,并且在急性应激刺激下容易造成行为绝望,因此C57BL/6小鼠可能适合作为急性应激抑郁模型动物。     

不同时间睡眠干扰所致小鼠的类抑郁样行为

目的研究不同时间睡眠干扰后所致的小鼠类抑郁样行为学表现。方法使用滚筒睡眠干扰仪对小鼠进行不同时间(5、10、15 d)睡眠干扰后,分别对各组动物进行自主活动测试实验、强迫游泳实验和悬尾实验。结果干扰5 d组与对照组比,自主活动总路程、平均速度、运动总时间减少(P<0.05),干扰10 d组与对照组比,自主活动总路程、平均速度、运动总时间减少(P<0.05)。干扰5 d后,小鼠强迫游泳、悬尾实验中各指标与对照组比无差异,干扰10 d组小鼠的游泳不动时间[(143.92±9.48)s]和悬尾不动时间[(127.89±6.33)s]均较对照组小鼠游泳不动时间[(128.50±6.63)s]和悬尾不动时间[(102.64±9.57)s]长(P<0.05),干扰15 d组小鼠的游泳不动时间[(143.08±8.13)s]和悬尾不动时间[(119.10±10.43)s]均较对照组小鼠游泳不动时间[(113.00±7.28)s]和悬尾不动时间[(89.55±9.07)s]长(P<0.05)。干扰5 d组、10 d组、15 d组与对照组比,体重均降低(P<0.05)。结论滚筒法睡眠干扰10、15 d可引起小鼠的类抑郁样行为学表现。     

百合总皂苷提取工艺及抗抑郁活性研究

本文研究百合总皂苷最佳提取工艺,继而采用AB-8大孔吸附树脂富集纯化百合总皂苷,并测试其抗抑郁活性。采用正交实验,考察乙醇浓度、提取次数、固液比及提取时间四个因素对该工艺的影响;采用小鼠悬尾实验和小鼠强迫游泳实验评价百合总皂苷的抗抑郁活性。确立了百合总皂苷的最佳提取工艺为:提取时间3h,乙醇浓度80%,固液比1∶10,提取次数为3次。在最佳提取工艺条件下,总皂苷提取率为1.24%。经过AB-8大孔树脂富集纯化总皂苷的含量达到62%以上。药理实验表明,百合总皂苷中剂量、小剂量能明显缩短小鼠悬尾的不动时间和游泳时间(P<0.05或者P<0.01),百合富集纯化的总皂苷部位具有较好的抗抑郁活性。     

对香豆酸对慢性束缚应激诱导小鼠抑郁样行为的作用*

目的: 探索对香豆酸(p-CA)对慢性束缚应激(CRS)诱导小鼠抑郁样行为的作用。方法: 实验分两批进行,第一批小鼠随机分成对照组(Control),慢性束缚应激组(CRS)和慢性束缚应激+p-CA组(CRS+p-CA),每组8只,其中慢性束缚应激小鼠每天接受4 h的束缚应激,连续束缚21 d,而对照组小鼠留在笼中不被打扰。第22日小鼠腹腔注射溶媒(10%吐温80)或p-CA(100 mg/kg),注射后1 h进行自发活动测试(LMA),注射后4 h进行强迫游泳测试(FST),注射后24 h进行悬尾测试。第二批小鼠随机分成慢性束缚应激组(CRS) ,慢性束缚应激+ANA-12(原肌球蛋白激酶B拮抗剂)组(CRS+ANA-12)和慢性束缚应激+p-CA组(CRS+ p-CA)慢性束缚应激+p-CA +ANA-12组(CRS+ p-CA +ANA-12),每组8只,4组小鼠每天接受4 h的束缚应激,连续束缚21 d。第22日小鼠腹腔注射溶媒(10%吐温80)或p-CA(100 mg/kg),ANA-12(0.5 mg/kg)在p-CA注射前30 min给药。注射后1 h进行自发活动测试(LMA),注射后2 h进行强迫游泳测试(FST),注射后24 h进行悬尾测试。结果: ①在实验一中,与Control组相比,CRS组小鼠强迫游泳和悬尾测试中不动时间显著性增多(P＜0.05);而与CRS组相比,CRS+ p-CA组小鼠不动时间显著性减少(P＜0.05,P＜0.01)。②在实验二中,与CRS组相比,CRS+ p-CA组小鼠强迫游泳和悬尾测试中不动时间显著性减少(P＜0.05);而与CRS+ p-CA组相比,CRS+ p-CA +ANA-12组小鼠强迫游泳和悬尾测试中不动时间显著性增多(P＜0.05)。结论: P-CA改善慢性束缚应激诱导小鼠抑郁样行为,TrkB受体可能介导了此作用。     

大孔树脂纯化瓜馥木总黄酮工艺及抗抑郁活性研究

本文采用大孔树脂纯化瓜馥木总黄酮,并评价其抗抑郁活性。以大孔树脂AB-8、HPD-600、HPD-826、X-5和D4006对瓜馥木总黄酮的吸附率和解吸率为指标筛选树脂种类,并对优选树脂的吸附特性和各影响因素进行研究,优化工艺条件。利用小鼠强迫游泳、小鼠悬尾和小鼠开野实验对瓜馥木总黄酮的抗抑郁活性进行了评价。结果表明AB-8具有较好的吸附率和解吸率,最佳纯化工艺为:上样流速为1.0 m L/min,树脂床用7 BV 5%乙醇除杂,再用8 BV 50%乙醇洗脱,洗脱流速1.0 m L/min,经AB-8大孔树脂纯化1次后,瓜馥木总黄酮含量为57.3%。瓜馥木总黄酮100 mg/kg剂量给药组能明显缩短小鼠强迫游泳和悬尾的不动时间,且该给药组小鼠的自主运动情况与阳性对照和空白之间没有显著差异。AB-8大孔树脂能较好地用于瓜馥木总黄酮的纯化,瓜馥木总黄酮具有明确的抗抑郁活性。     

罗布麻叶总黄酮提取物促进小鼠抗抑郁基因CREB、BDNF的表达

罗布麻是中国药典收录的传统中药,本研究提取它的主要有效成分罗布麻总黄酮,采用经典抗抑郁评价模型小鼠强迫游泳实验对罗布麻叶总黄酮进行抗抑郁活性评价.试验中给小鼠罗布麻叶总黄酮提取物25 mg/kg、50 mg/kg和100 mg/kg后,观察罗布麻叶总黄酮对小鼠强迫游泳不动时间的影响,结果显示罗布麻总黄酮提取物能显著缩短小鼠强迫游泳不动时间(P<0.05),药效与氟西汀相似,表明罗布麻具有明显的抗抑郁活性.在此基础上,应用皮质酮损伤的PC12细胞模型,采用荧光相对定量RT-PCR法检测罗布麻对皮质酮损伤的PC12细胞中脑内脑源性神经营养因子(BDNF)和环磷酸腺苷反应元件结合蛋白(CREB)表达水平的影响.结果表明,皮质酮处理后PC12细胞中BDNF、CREB基因的表达量最低,罗布麻处理后,表达量显著增加,较处理前增加了近十倍,且呈剂量依赖性.本研究结果提示罗布麻抗抑郁机制可能是通过(AC-cAMP-CREB)信号通路促进BDNF、CREB的基因表达而发挥的.     

Apelin receptor(APJ)拮抗剂F13A对小鼠抑郁样行为的影响及起效时间*

目的:明确apelin receptor(APJ)拮抗剂F13A对小鼠抑郁样行为的影响及起效时间。方法:实验小鼠随机分成对照组(Control),F13A组(F13A)和氯胺酮组(ketamine),每组9只,对照组小鼠腹腔注射生理盐水(10 ml/kg,ip)+侧脑室注射生理盐水(每职1μl,i.c.v),F13A组小鼠腹腔注射生理盐水(10 ml/kg,ip)+侧脑室注射F13A(6 μg/μl,i.c.v),氯胺酮组小鼠腹腔注射氯胺酮(10 ml/kg, 2 mg/ml,ip)+侧脑室注射生理盐水(1μl,i.c.v);实验分三批进行,第一批实验在注射后30 min,进行第一次强迫游泳测试(FST1),FST1后24 h进行第二次强迫游泳测试(FST2);第二批实验在注射后30 min进行第一次自发活动测试(LMT1),LMT1前24 h进行自发活动习惯化,LMT1后24 h进行第二次自发活动测试(LMT2);第三批实验注射后30 min进行FST1,FST1前24 h进行强迫游泳应激(FSS),FST1后24 h进行第二次强迫游泳测试(FST2)。 结果:与对照组比较,在无FSS时,氯胺酮组小鼠不动时间显著性减少(P﹤0.01),而F13A组小鼠无明显变化;在FST2中,F13A组小鼠不动时间显著性增加(P﹤0.01),而氯胺酮组小鼠无显著性差异;在LMT1和LMT2中各组小鼠活动度均无显著性差异;在经历FSS后,在FST1中氯胺酮组、F13A组小鼠不动时间均显著性减少(P﹤0.01);在FST2中,F13A组小鼠的不动时间显著性减少(P﹤0.05),而氯胺酮组小鼠无显著性差异(P＞0.05)。结论:APJ受体拮抗剂F13A在强迫游泳测试中发挥快速起效(30 min)且持久作用(24 h)的抗抑郁样潜力,并且这种作用可能与应激有关。     

莫扎特K448奏鸣曲高频段声波对小鼠抑郁模型干预治疗的分析

目的 建立C57BL/6小鼠抑郁模型,初步探究莫扎特K448奏鸣曲中的高频段声波改善C57BL/6小鼠抑郁症状的效果。方法 1)慢性应激模型的建立:小鼠依据自主活动实验结果剔除活动次数差异较大者,其余分为空白组(n=10)、模型组(n=36),模型组经历5周慢性温和不可预知刺激(chronic unpredictable and mildstress,CUMS),建立小鼠抑郁模型。(2)治疗干预:造模成功后,将模型组小鼠随机均衡分为模型对照组(n=12)、氟西汀组(n=12)和音乐组(n=12)。氟西汀组每天腹腔注射盐酸氟西汀溶液(10 mg/kg),其余两组注射等量的生理盐水。音乐组每天进行2 h高频音乐干预,其余两组不进行音乐干预。干预持续2周。(3)效果评价:实验前3 d及实验中每周称量体重并记录,实验第1周、第5周、第7周进行悬尾实验(tail suspension test,TST)和强迫游泳实验(forced swimming test,FST)。第7周行为学实验结束后,取小鼠脑组织制备匀浆,通过酶联免疫吸附法(enzymelinked immunosorbent assay,ELISA)测定脑源性神经营养因子(brain derived neurotrophic factor,BDNF)含量。结果1)成功构建CUMS小鼠模型。第5周模型组小鼠悬尾不动时间明显增加,差异有显著性(P<0.01),强迫游泳不动时间增加,差异有显著性(P<0.05)。(2)氟西汀组与模型对照组相比,悬尾实验不动时间明显缩短,差异有显著性(P<0.01),强迫游泳实验不动时间缩短,差异无显著性(P>0.05);音乐组与模型对照组相比,悬尾不动时间缩短,差异有显著性(P<0.05),强迫游泳实验不动时间无明显改变,差异无显著性(P>0.05)。模型对照组与空白组小鼠相比,脑组织匀浆中的BDNF含量明显降低,差异有显著性(P<0.01);氟西汀组与模型对照组相比,脑组织匀浆中的BDNF含量明显回升,差异有显著性(P<0.01),但音乐组与模型对照组相比,其差异无显著性(P>0.05)。结论 莫扎特K448奏鸣曲高频段声波可一定程度优化小鼠抑郁模型的治疗作用。     

金钗石斛提取物对慢性不可预见应激模型小鼠的抗抑郁作用

为了探讨金钗石斛提取物对慢性不可预见应激模型小鼠的抗抑郁作用,将BALB/c小鼠分为6组,即正常组、模型组、阳性药组(帕罗西汀),金钗石斛低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组,灌胃给药两周后,除正常组外,其他组给予慢性不可预见性应激造模35天。造模结束后,通过糖水偏爱、新奇抑制摄食、强迫游泳实验和悬尾实验检测其行为学改变,采用LC-MS/MS测定各组小鼠应激后海马及皮层单胺类神经递质包括多巴胺(dopamine,DA)和5-羟色胺(5-hydroxytryptamine,5-HT)的含量改变。结果显示,与正常组相比,模型组小鼠糖水偏爱指数下降(P0.01);与模型组比较,金钗石斛各剂量组可显著逆转模型小鼠出现的糖水偏爱指数下降(P0.01),其作用与阳性药帕罗西汀相当;与正常组相比,模型组小鼠新奇抑制摄食潜伏期延长(P0.01);与模型组比较,金钗石斛各剂量组均可显著缩短新奇抑制摄食潜伏期(P0.01);与正常组相比,模型组小鼠悬尾的不动时间明显延长(P0.01),与模型组比较,帕罗西汀及200 mg/kg金钗石斛均可缩短悬尾的不动时间(P0.05);与正常组相比,模型小鼠在强迫游泳实验中不动时间无明显延长,各给药组的不动时间也未见明显改变(P0.05)。与正常组相比,模型组小鼠皮层和海马中的DA和5-HT含量明显减少(P0.05);帕罗西汀能使模型小鼠海马和皮层DA、海马5-HT含量明显增加(P0.05);金钗石斛低、高剂量组皮层DA含量与模型组相比显著性升高(P0.05),金钗石斛中、高剂量组海马DA含量与模型组相比显著性升高(P0.05);金钗石斛高剂量组皮层和海马5-HT含量显著高于模型组(P0.05),但金钗石斛中剂量组仅海马5-HT含量显著高于模型组(P0.01)。以上结果提示,慢性不可预见应激可导致小鼠的类抑郁样行为出现,而金钗石斛提取物能有效改善慢性不可预见应激模型动物的抑郁样行为学表现,并提高小鼠脑内的DA和5-HT水平。     

The antianxiety-like effect of astaxanthin extracted from Paracoccus carotinifaciens

Astaxanthin is a red carotenoid pigment and is widely found in living organisms. Astaxanthin has a potent antioxidative ability and has been reported as having various biological effects on the central nerve system, such as a protective effect against ischemia/reperfusion injury and improvement in cognitive function. In this study, to investigate the effects of astaxanthin on anxiety and depression, we performed some behavioral trials including the elevated plus maze test, hole-board test, forced swim test, and tail suspension test. Astaxanthin (100 and 300 mg/kg/day for 10 days, p.o.) significantly increased the time spent in open arms in the elevated plus maze test and increased the head-dipping count and duration in the hole-board test. On the other hand, astaxanthin (10, 100, 300, and 500 mg/kg/day for 10 days, p.o.) did not change the immobility time in the forced swim test or the tail suspension test. In conclusion, in mice, astaxanthin exerted anxiolytic-like effects, but not antidepressant-like effects.     

Evaluation of antidepressant-like activity of aqueous and ethanolic extracts of Terminalia bellirica Roxb. fruits in mice

The present study was undertaken to investigate the effect of aqueous and ethanolic extracts of T. bellirica on depression in mice using forced swim test (FST) and tail suspension test (TST). The extracts were administered orally for 10 successive days in separate groups of Swiss young male albino mice. Aqueous extract (50, 100 and 200 mg/kg) in a dose-dependent manner and ethanolic extract (100 mg/kg) significantly reduced the immobility time of mice in both FST and TST. The extracts were without any significant effect on locomotor activity of mice. The efficacies of aqueous extract (200 mg/kg) and ethanolic extract (100 mg/kg) were found to be similar to that of imipramine (15 mg/kg, po) and fluoxetine (20 mg/kg, po) administered for 10 successive days. Both extracts reversed reserpine-induced extension of immobility period of mice in FST and TST. Prazosin (62.5 microg/kg, ip; an alpha1-adrenoceptor antagonist), sulpiride (50 mg/kg, ip; a selective D2 receptor antagonist) and p-chlorophenylalanine (100 mg/kg, ip; an inhibitor of serotonin synthesis) significantly attenuated the aqueous and ethanolic extract-induced antidepressant-like effect in TST. Thus, both the aqueous and ethanolic extracts of T. bellirica elicited a significant antidepressant-like effect in mice by interaction with adrenergic, dopaminergic and serotonergic systems.     

Anti-depressant-like activity of a novel serotonin type-3 (5-HT3) receptor antagonist in rodent models of depression

N-Cyclohexyl-3-methoxyquinoxalin-2-carboxamide (QCM-13), a novel 5-HT3 antagonist identified from a series of compounds with higher pA2 (7.6) and good log P (2.91) value was screened in rodent models of depression such as forced swim test (FST), tail suspension test (TST), interaction studies with standard anti-depressants and confirmatory studies such as reversal of parthenolide induced depression and reserpine induced hypothermia. In FST (2 and 4 mg/kg) and TST (2 and 4 mg/kg), QCM-13 significantly reduced the duration of immobility in mice without affecting the base line locomotion. QCM-13 (2 and 4 mg/kg) was also found to have significant interaction with standard anti-depressants (fluoxetine and bupropion in FST and TST respectively). Further, reversal of parthenolide induced depression in mice and reserpine induced hypothermia in rat models indicate the serotonergic influence of QCM-13 for anti-depressant potential.     

Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression

Mitragyna speciosa Korth. leaves have been used for decades as a traditional medicine to treat diarrhea, diabetes and to improve blood circulation by natives of Malaysia, Thailand and other regions of Southeast Asia. Mitragynine is the major active alkaloid in the plant. To date, the role of mitragynine in psychological disorders such as depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of mitragynine in the mouse forced swim test (FST) and tail suspension test (TST), two models predictive of antidepressant activity and the effect of mitragynine towards neuroendocrine system of hypothalamic-pituitary-adrenal (HPA) axis by measuring the corticosterone concentration of mice exposed to FST and TST. An open-field test (OFT) was used to detect any association of immobility in the FST and TST with changes in motor activity of mice treated with mitragynine. In the present study, mitragynine at dose of 10 mg/kg and 30 mg/kg i.p. injected significantly reduced the immobility time of mice in both FST and TST without any significant effect on locomotor activity in OFT. Moreover, mitragynine significantly reduced the released of corticosterone in mice exposed to FST and TST at dose of 10 mg/kg and 30 mg/kg. Overall, the present study clearly demonstrated that mitragynine exerts an antidepressant effect in animal behavioral model of depression (FST and TST) and the effect appears to be mediated by an interaction with neuroendocrine HPA axis systems.     

Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice

This study investigated the effect of berberine (BER) in the mouse forced swim test (FST) and in the tail suspension test (TST), two models predictive of antidepressant activity. We also investigated the antidepressant-like mechanism of BER by the combination of the desipramine [DES, an inhibitor of reuptake of noradrenaline (NA) and serotonin (5-HT)], maprotiline (MAP, selective NA reuptake inhibitor), fluoxetine (FLU, selective 5-HT reuptake inhibitor) and moclobemide [MOC, monoamine oxidase (MAO) A inhibitor). Then we further measured the levels of monoamines [NA, dopamine (DA) and 5-HT) in mice striatum, hippocampus and frontal cortex. The results show that BER (10, 20 mg/kg, p.o.), significantly reduced the immobility time during the FST and the TST. The immobility time after treatment with BER (20 mg/kg, p.o.) in FST was augmented by DES, FLU and MOC, and not affected by MAP. Furthermore, BER (20 mg/kg, p.o.) increased NA and 5-HT levels in the hippocampus and frontal cortex. Our findings support the view that BER exerts antidepressant-like effect. The antidepressant-like mechanism of BER may be related to the increase in NA and 5-HT levels in the hippocampus and frontal cortex.     

Acute Treatment with a Novel TRPC4/C5 Channel Inhibitor Produces Antidepressant and Anxiolytic-Like Effects in Mice

Transient receptor potential canonical (TRPC) channels are widely expressed in brain and involved in various aspects of brain function. Both TRPC4 and TRPC5 have been implicated in innate fear function, which represents a key response to environmental stress. However, to what extent the TRPC4/C5 channels are involved in psychiatric disorders remains unexplored. Here, we tested the antidepressant and anxiolytic-like effects of a newly identified TRPC4/C5 inhibitor, M084. We show that a single intraperitoneal administration of M084 at 10 mg/kg body weight to C57BL/6 male mice significantly shortened the immobility time in forced swim test and tail suspension test within as short as 2 hours. The M084-treated mice spent more time exploring in illuminated and open areas in light/dark transition test and elevated plus maze test. In mice subjected to chronic unpredictable stress, M084 treatment reversed the enhanced immobility time in forced swim test and decreased the latency to feed in novelty suppressed feeding test. The treatment of M084 increased BDNF expression in both mRNA and protein levels, as well as phosphorylation levels of AKT and ERK, in prefrontal cortex. Our results indicate that M084 exerts rapid antidepressant and anxiolytic-like effects at least in part by acting on BDNF and its downstream signaling. We propose M084 as a lead compound for further druggability research.     

Antidepressant-like effect of 17beta-estradiol: involvement of dopaminergic, serotonergic, and (or) sigma-1 receptor systems

17beta-estradiol has been reported to possess antidepressant-like activity in animal models of depression, although the mechanism for its effect is not well understood. The present study is an effort in this direction to explore the mechanism of the antidepressant-like effect of 17beta-estradiol in a mouse model(s) of behavioral depression (despair behavior). Despair behavior, expressed as helplessness to escape from a situation (immobility period), as in a forced swim test in which the animals are forced to swim for a total of 6 min, was recorded. The antiimmobility effects (antidepressant-like) of 17beta-estradiol were compared with those of standard drugs like venlafaxine (16 mg/kg, i.p.). 17beta-estradiol produced a U-shaped effect in decreasing the immobility period. It had no effect on locomotor activity of the animal. The antidepressant-like effect was comparable to that of venlafaxine (16 mg/kg, i.p.). 17beta-estradiol also exhibited a similar profile of antidepressant action in the tail suspension test. When coadministered with other antidepressant drugs, 17beta-estradiol (5 microg/kg, i.p.) potentiated the antiimmobility effect of subeffective doses of fluoxetine (5 mg/kg, i.p.), venlafaxine (2 mg/kg, i.p.), or bupropion (10 mg/kg, i.p.), but not of desipramine (5 mg/kg, i.p.) or tranylcypromine (2 mg/kg, i.p.), in the forced swim test. The reduction in the immobility period elicited by 17beta-estradiol (20 microg/kg, i.p.) was reversed by haloperidol (0.5 mg/kg, i.p.; a D(2) dopamine receptor antagonist), SCH 23390 (0.5 mg/kg, i.p.; a D(1) dopamine receptor antagonist), and sulpiride (5 mg/kg, i.p.; a specific dopamine D(2) receptor antagonist). In mice pretreated with (+)-pentazocine (2.5 mg/kg, i.p.; a high-affinity sigma-1 receptor agonist), 17beta-estradiol (5 microg/kg, i.p.) produced a synergistic effect. In contrast, pretreatment with progesterone (10 mg/kg, s.c.; a sigma-1 receptor antagonist neurosteroid), rimcazole (5 mg/kg, i.p.; another sigma-1 receptor antagonist), or BD 1047 (1 mg/kg, i.p.; a novel sigma-1 receptor antagonist) reversed the antiimmobility effects of 17beta-estradiol (20 microg/kg, i.p.). Similarly, in mice pretreated with a subthreshold dose of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A serotonin receptor agonist), 17beta-estradiol (5 microg/kg, i.p.) produced an antidepressant-like effect. These findings demonstrate that 17beta-estradiol exerted an antidepressant-like effect preferentially through the modulation of dopaminergic and serotonergic receptors. This action may also involve the participation of sigma-1 receptors.     

An experimental study of the antidepressive properties of captopril]

Captopril, as well as amitriptyline, was shown to enhance apomorphine-induced stereotype in mice. At doses, which failed to modify the effect of apomorphine, both substances reversed the inhibitory action of sulpiride and haloperidol on stereotypical behaviour. Treatment with captopril (25 mg/kg) did not modify the open-field behaviour, but significantly reduced the immobility in the forced swim test (20 mg/kg) Dopaminergic link was suggested to be involved in the CNS effect of captopril.     

Discovery and synthesis of novel 3-phenylcoumarin derivatives as antidepressant agents

A series of 3-phenylcoumarins were synthesized and screened for potential antidepressant activity by tail suspension test (TST) in mice. Three compounds (6, 7 and 13) exhibited impressive antidepressant activity, measured in terms of percentage decrease in immobility duration (% DID). In addition, the active antidepressant compounds were subsequently studied at their most effective dose and activity of these compounds were confirmed in forced swimming test (FST) animal model, in which the compounds at a low dose of 0.5 mg/kg significantly decreased the immobility time and exhibited greater efficacy than the reference standards fluoxetine and imipramine. The potent compounds did not show any neurotoxicity in the rotarod test and the preliminary results are promising enough to warrant further studies around this scaffold.