吲哚衍生物I_(20)的抗焦虑作用及机制研究

目的　研究外周型苯二氮卓受体配基吲哚衍生物I2 0的抗焦虑作用及作用机制。方法　在小鼠高架十字迷宫模型和小鼠明暗箱模型上评价I2 0 的抗焦虑活性 ,用放免法测定给予不同剂量的I2 0 在不同时间点大鼠血清中神经类固醇孕酮的含量。结果　I2 0 (1mg·kg-1,ip)能增加小鼠在开臂内运动时间百分率和小鼠穿箱次数 ,在小鼠高架十字迷宫与明暗箱模型上显示出抗焦虑作用 ;I2 0 在实验剂量下 (2 0mg·kg-1,ip)对小鼠自主活动性无影响 ,表明该化合物在抗焦虑的剂量下无镇静的副作用。放免测定结果表明 ,I2 0 能剂量依赖与时间依赖地增加大鼠血清中孕酮的含量。结论　I2 0 可能是通过与外周型苯二氮卓受体结合 ,增加体内神经类固醇孕酮的释放 ,间接调控GABAA 受体的功能来发挥抗焦虑作用     

中国林蛙卵油的抗焦虑作用

目的研究中国林蛙卵油 (eggoilofRanatemporariachensinensisDavid ,EORTCD)的抗焦虑作用。方法应用高架十字迷路和小鼠爬梯实验评价中国林蛙卵油的抗焦虑活性及其量效、时效关系。结果与对照组比较 ,EORTCD 2 0、4 0 g·kg-1能显著延长大鼠在十字迷路开放通路连续停留时间 ,增加大鼠进入开放通路次数 ,而对封闭通路连续停留时间和进入封闭通路次数无明显影响 ;小鼠爬梯实验中 ,EORTCD 1 4～5 6g·kg-1组小鼠站立数明显减少而爬梯数无显著差异 ;EORTCD抗焦虑时效实验表明在给药后 3 0、60min抗焦虑活性较强 ;γ 氨基丁酸 (γ aminobutyricacid ,GABA) 5 0、1 0 0mg·kg-1分别与EORTCD 1 2 g·kg-1联合给药组的小鼠站立数显著降低而爬梯数无显著减少 ,且比单独给予EORTCD组小鼠站立数少。结论中国林蛙卵油有明显抗焦虑作用。     

黄芩苷对γ-氨基丁酸受体和抗焦虑症作用研究

目的观察黄芩苷与γ-氨基丁酸（GABA）受体的关系及其所具有的抗焦虑作用。方法采用同位素标记GABA受体结合实验观察黄芩苷与GABA受体的关系;采用高台十字迷宫实验和四孔箱实验观察动物服用黄芩苷后行为的改变。结果 GABA受体竞争结合试验显示,黄芩苷可竞争性抑制50%GABA受体苯二氮类结合浓度（IC50）为（117.62±8.50）μmol·L-1,抑制结合常数（Ki）为（77.10±4.79）μmol·L-1。黄芩苷可增加实验动物进入十字迷宫开放侧次数,百分率和滞留时间,减少在四孔箱中探头和竖身的次数。这些变化与黄芩苷剂量有明显的关系,可被GABA受体阻断剂Ro 15-1788阻断。结论黄芩苷是GABA结合位点的配体,具有一定的抗焦虑作用。     

谷维素和维生素B1增强地西泮的抗焦虑作用

目的研究地西泮、谷维素和维生素B1按1∶32∶8的比例合用后的抗焦虑作用,并同地西泮比较.方法采用大、小鼠高架十字谜宫模型和大鼠五甲烯四氮唑辨别效应对抗模型.结果在大、小鼠高架十字迷宫实验中,地西泮与谷维素和维生素B1合用后,大、小鼠在开放臂停留时间百分率明显增加,表现出明显的抗焦虑作用;而且其在开放臂停留时间百分率的增加,明显高于单独使用与其含量相等的地西泮的作用.在大鼠五甲烯四氮唑辨别效应对抗实验中,合用后对抗大鼠五甲烯四氮唑辨别效应的ED50值为23.4 mg·kg-1,其地西泮含量为0.6 mg·kg-1,远低于地西泮单方的ED50值3.5mg·kg-1.结论谷维素和维生素B1具有增强地西泮的抗焦虑作用.     

核黄素四丁酸酯抗焦虑作用的药效学研究

目的考察核黄素四丁酸酯(RTB)的抗焦虑作用。方法以地西泮和丁螺环酮为阳性对照药,采用小鼠高架十字迷宫和新型食物消耗实验,评价RTB抗焦虑作用;采用转棒实验测定RTB对小鼠肌肉协调运动能力的影响。结果与空白对照组比较,RTB不影响小鼠在高架十字迷宫中的入臂总次数,但在20和40 mg.kg-1的剂量下明显增加开臂进入次数百分比和在开臂中滞留时间百分比;在新型食物消耗实验中,RTB在剂量为40和80 mg.kg-1时,明显增加小鼠单位体重的食物消耗量;转棒实验中,与阳性药物比较,RTB组明显降低了小鼠的跌落率。结论 RTB具有抗焦虑的作用,且不影响小鼠的活动能力和肌肉协调性。     

天麻及其酚类化合物对小鼠的抗焦虑作用

天麻Gastrodia elata Blume的抗焦虑作用研究鲜有报道。因此,作者进行了以下试验,研究该植物根茎水提取物(AEGE)以及所含的酚类化合物4-羟基苄醇(HA)和4-羟基苯甲醛(HD)对小鼠在高架十字迷宫实验中的抗焦虑作用,并观察了AEGE与氟马西尼或WAY 100635同服对AEGE抗焦虑作用的影响。选用雄性ICR小鼠。在开场实验中,小鼠给以AEGE50、100、200、400 mg/kg,HA或HD5、10、25、50、100 mg/kg,记录给药1h后小鼠5min内水平运动能力。在高架十字迷宫(EPM)实验中,记录给以试药(剂量同上)1h后,小鼠5min内进入开臂或闭臂的次数与停留时间,以…     

钩吻素子对大鼠焦虑行为的影响

目的进一步明确钩吻素子是否具有抗焦虑作用。方法以大鼠高架十字迷宫实验为动物模型,评价钩吻素子单次皮下注射给药和连续皮下注射给药的抗焦虑活性及特点。结果钩吻素子能显著增加大鼠进入高架十字迷宫开臂次数和在开臂的停留时间百分率(P<0.05,P<0.01);钩吻素子在实验剂量下对大鼠自主运动活性无影响(P>0.05)。结论钩吻素子可能具有抗焦虑作用。     

组胺与扑尔敏对焦虑的影响

目的观察和分析组胺与扑尔敏对焦虑的影响。方法选用小鼠高架十字迷宫实验和小鼠明暗箱实验分别测定各组小鼠进入开放臂和封闭臂的总次数(OE+CE)、进入开放臂次数百分比(OE%)、开放臂停留时间比例(OT%)、探究次数(HT)和封闭臂后腿直立次数(RT)、明暗箱中的穿箱次数(TT)和在明箱停留时间的百分比(LT%)。结果剂量为4.44×l0-6g·kg-1的组胺(HA)能显著减少小鼠的OT%(P>0.05);4.00×l0-3g·kg-1的扑尔敏以及同剂量的扑尔敏加4.44×l0-6g·kg-1HA能显著增加小鼠的OE+CE、OE%、OT%、TT、LT%(P>0.01)。结论扑尔敏具有抗焦虑的作用,外周给予一定量的HA可以通过H1受体发挥促进焦虑的作用。     

缬草素抗焦虑作用及其机制的初探

目的研究缬草素的抗焦虑作用,并分析其可能的作用机制。方法以大鼠高架十字迷宫实验和开场实验为动物模型,考察缬草素的抗焦虑活性;用酶联免疫吸附法(ELISA)测定大鼠血清皮质酮的水平。结果缬草素(10mg.kg-1)能增加大鼠在开臂内运动时间和次数百分率,并且提高大鼠在开场中央区的次数,在大鼠高架十字迷宫与开场模型上显示出抗焦虑作用;酶联免疫吸附法表明:缬草素能降低大鼠血清皮质酮水平。结论缬草素具有明显的抗焦虑作用,机制可能与调节下丘脑-垂体-肾上腺轴功能有关。     

核黄素四丁酸酯抗焦虑作用的药效学分析

目的了解核黄素四丁酸酯的抗焦虑作用。方法以空白和地西泮为对照,采用小鼠高架十字迷宫实验,评价RTB抗焦虑作用。结果与空白组比较,各给药组的总入臂次数(OE+CE)均有提高,但未有统计学差异(P>0.05),提示各组药物均未改变动物的活动能力。地西泮和RTB均能提高小鼠的OE%值,但未见RTB对小鼠的OE%有统计学差异(P>0.05),而地西泮能显著提高小鼠的OE%。与空白组比,RTB小剂量组能显著提高小鼠的OT%,并有统计学差异(P<0.05)。结论 RTB具有抗焦虑作用,且不影响小鼠的运动活力。     

Anxiolytic-Like Effect of baicalin and its additivity with other anxiolytics

Baicalin, a naturally occurring flavonoid, was previously reported to exert anxiolytic-like effects in the Vogel conflict test. In the present study, the anxiolytic effects of baicalin alone and in combination with other anxiolytics were tested in mice using the elevated plus-maze (EPM). Baicalin treatment (7.5 - 30 mg/kg) significantly increased entries into and time spent in open arms, indicative of an anxiolytic-like effect. Motor-depressive and myorelaxant side effects commonly associated with anxiolytics were not observed with baicalin at effective anxiolytic doses in the hole-board and horizontal wire tests, respectively. Co-administration of baicalin (3.75 mg/kg) with dl-tetrahydropalmatine ( dl-THP; 0.25 mg/kg), an anxiolytic-hypnotic alkaloid, both at sub-effective doses, induced an additive effect resulting in considerable anxiolysis. Similarly, an additive anxiolytic-like effect was observed with baicalin (3.75 mg/kg) and diazepam (DZ; 0.5 mg/kg). Results obtained from this study demonstrate the potential of baicalin as a candidate anxiolytic and its possible application in multidrug therapy. Abbreviations. BZS:benzodiazepine-binding site EPM:elevated plus-maze DZ:diazepam GABA (A):type A gamma-aminobutyric acid dl-THP: dl-tetrahydropalmatine.     

Anxiolytic-like effect of saiboku-to, an oriental herbal medicine, on histaminergics-induced anxiety in mice

Effect of saiboku-to, an oriental herbal medicine, on anxiety in mice was investigated using a light/dark test. Anxiogenic- and anxiolytic-like effects were evaluated on the basis of shortened and prolonged time spent in the light zone of the test. Subacute administration (once a day for 7 days) of saiboku-to (0.5-2.0 g/kg, p.o.) induced anxiolytic-like effect. To assess the effect of saiboku-to on brain histaminergic system in a state of anxiety, Compound 48/80 (1.0 microg/2 microl, i.c.v.), a non-neuronal mast cell histamine releaser, or thioperamide (10.0 mg/kg, i.p.), a neuronal histamine releaser possessing the inhibitory effect of histamine H(3) autoreceptors, induced decrease in the time spent in the light zone by co-injection with cimetidine (10.0 microg/2 microl, i.c.v.), a H(2) inhibitor, suggesting anxiety-like effect. These histaminergics-induced experimental anxieties were inhibited by pre-treatment with subacute administration of saiboku-to, as well as single treatment with diazepam. The results suggest that saiboku-to exhibits anxiolytic-like effect closely related to histaminergic system in the brain.     

The effects of angelica essential oil in three murine tests of anxiety

The effects of angelica essential oil in three assays predictive of anxiolytic activity in male mice were studied, with diazepam as a positive anxiolytic control. In the elevated plus-maze test, compared to the positive control diazepam, angelica essential oil (30.0 mg/kg, PO) had a modest anxiolytic-like effect (increased the percentage of open-arm time and reduced the percent protected head dips). In the light/dark test, angelica essential oil (30.0 mg/kg) prolonged the time spent in the light area without altering the locomotor activity of the animals. In the stress-induced hyperthermia test, 60 and 70 min after drug administration, rectal temperature was measured twice, angelica essential oil at the dose of 30.0 mg/kg inhibited stress-induced hyperthermia. Thus, these findings indicate that angelica essential oil, as does diazepam, exhibits an anxiolytic-like effect. Further studies will be required to assess the generality of the present findings to other species and behavioural paradigms.     

Anxiolytic-like effect of paeonol in mice

The present study in mice compared the putative anxiolytic-like effect of paeonol, a phenolic component from the root bark of Paeonia moutan, with the benzodiazepine diazepam in the elevated plus maze and the light/dark box-test. The comparison was also with regard to locomotor activity (open-field test) and myorelaxant potential (inclined plane test). As with 2 mg/kg diazepam, paeonol (at 17.5 mg/kg) increased the percentage of time spent on open arms in the elevated plus maze and increased the time spent in the light area of the light/dark box (at 8.75 and 17.5 mg/kg). Since paeonol, in contrast to diazepam, had no effect on either the number of squares entered in the open-field test or in the inclined plane test, its side-effect profile is considered as superior to the benzodiazepine.     

Anxiolytic-like effect of asiaticoside in mice

The putative anxiolytic activity of asiaticoside was examined in male mice by using a number of experimental paradigms of anxiety, with diazepam being as a positive anxiolytic control. In the elevated plus-maze test, diazepam (1 and 2 mg/kg) or asiaticoside (5 or 10 mg/kg) increased the percentage of entries into open arms and of time spent on open arms. In the light/dark test, as with 1 mg/kg diazepam, asiaticoside (10 and 20 mg/kg) increased the time spent in the light area and the movement in the light area without altering the total locomotor activity of the animals. In the hole-board test, asiaticoside at 10 mg/kg significantly increased head-dipping counts and duration as well as diazepam (0.3 mg/kg). Thus, these findings indicated that asiaticoside exhibited an anxiolytic-like effect. Further studies will be required to assess the generality of present findings to other species and behavioural paradigms.     

Evaluation of anxiolytic-like effects of some short-acting benzodiazepine hypnotics in mice

Anxiolytic-like effects of some short-acting benzodiazepine hypnotics were examined with experimental paradigms of anxiety using an elevated plus-maze in male ICR mice. Diazepam was used as a positive control. The drug at a dose of 1 mg/kg significantly increased the percentage of time spent in the open arms and percentage of the number of open arm entries in the elevated plus-maze. Triazolam, brotizolam, rilmazafone, and lormetazepam also showed an anxiolytic-like effect as indicated by the significant increase in the percentage of time spent in the open arms and percentage of the number of open arm entries. Effects of short-acting benzodiazepine hypnotics used in the study were more potent than those of diazepam. In addition, the doses affecting the elevated plus-maze by benzodiazepine hypnotics were much smaller than those that showed muscle-relaxant activity measured by the rotarod test, indicating that anxiolytic-like effects of benzodiazepine hypnotics had high specificity and selectivity.     

Comparison of routes of administration and time course effects of zacopride and buspirone in mice using an automated light/dark test

The behavioral effects of zacopride and buspirone were assessed in mice in a fully automated 2-compartment light/dark test. A significant increase in time mice spent in the lit area was used as an indication of anxiolytic-like action. Doses of zacopride from 0.0001 to 17.8 mg/kg, IP, and buspirone from 3.16 to 17.8 mg/kg, IP, produced significant increases in time mice spent in the lit area of the chamber. In addition, zacopride and buspirone were compared for oral potency and for duration of action after IP and PO administration. Zacopride and buspirone produced anxiolytic-like activity between doses of 0.001 to 100.0 mg/kg, PO, and 10.0 to 56.2 mg/kg, PO, respectively. The duration of effect of buspirone was 2 to 4 h after IP or PO administration, while that for zacopride was ≥16 h by either route of administration. Thus, when compared for anxiolytic-like effects in this test, zacopride is a more potent and longer acting agent than buspirone.     

Riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines

In this study, we investigated the anxiolytic-like effect of riluzole using three different innate anxiety models in rats. In the elevated plus-maze test, riluzole significantly increased the time spent in, and entries into, the open arm after 60 min administration. This finding was supported by results obtained from light/dark and open-field tests. The magnitude of the anxiolytic-like effects of riluzole in each of the behavioral models was similar to those produced by a benzodiazepine, diazepam, suggesting that riluzole has a robust anxiolytic-like activity in rats. To clarify the involvement of sodium channels in this anxiolytic activity, we examined the effect of a co-administered sodium channel activator, veratrine. The anxiolytic-like action of riluzole was diminished by veratrine in the elevated plus-maze, light/dark and open-field tests. Based on these results, it is suggested that the anxiolytic mechanism of riluzole is clearly distinct from that of diazepam. In addition, to examine whether riluzole directly and non-selectively affected the GABA^A-benzodiazepine receptor complex, we performed three behavioral tests (footprint analysis, Y-maze test and the ethanol-induced sleeping time test) that are closely related to the GABA^A-benzodiazepine pathways. In contrast to diazepam, riluzole produced no significant effects in these tests. Here, we provide the first report demonstrating that riluzole produces distinct anxiolytic-like effects in rats without the adverse effects associated with benzodiazepines.     

Effects of taurine on rat behaviors in three anxiety models

In our previous studies using an elevated plus-maze test in mice, taurine was shown to present an anxiolytic-like effect after single and repeated administration. The aim of the present study was to investigate the anxiolytic and behavioral effects of taurine on rats in the open field, hole-board, and social interaction test compared to the positive control diazepam. Taurine (14, 42, and 126 mg/kg, i.p.) was administered 30 min before the tests. In the social interaction and hole-board tests, taurine (42 mg/kg) significantly increased social interaction time and the number and duration of head-dipping. In the open field test, taurine (126 mg/kg, i.p.) presented anxiolytic-like effects by increasing the number of center entries, time spent in the central area and the anti-thigmotactic score while having no effect on the locomotor activity. Results from these experiments suggest that taurine produces an anxiolytic-like effect in these animal models and may act as a modulator or anti-anxiety agent in the central nervous system.