共查询到20条相似文献,搜索用时 314 毫秒
1.
《中国药理学通报》2016,(1)
目的以慢性孕前应激诱导建立产后抑郁症小鼠模型,研究越鞠甘麦大枣汤(越甘)对产后抑郁母鼠的快速抗抑郁作用,并从海马AKT/m TOR信号通路角度探讨产后抑郁的发病机制以及中药越甘快速治疗产后抑郁症的作用机制。方法将32只Bal b/c母鼠随机分为2组,空白对照组,不给予任何刺激;孕前应激组,小鼠给予慢性束缚刺激。3周后慢性孕前应激组小鼠♀♂合笼交配怀孕,于分娩后3周检测母鼠悬尾测试(tail suspension test,TST)。将产后抑郁模型组母鼠随机分为3组:模型组、越甘组(YG)、氯胺酮组。检测药物对产后抑郁母鼠的干预作用,并取母鼠海马检测AKT、m TOR磷酸化蛋白(phosphorylation protein)以及总蛋白的表达。结果产后3周,与对照组比较,PPD模型组在悬尾测试中的绝望状态不动时间明显增加(P<0.01)。与对照组相比,PPD模型组母鼠海马AKT、m TOR磷酸化蛋白表达均下调,且差异具有显著性(P<0.01,P<0.01)。单次给予越甘或氯胺酮24 h之后,PPD模型母鼠悬尾测试的绝望不动时间明显降低(P<0.01,P<0.01),并且海马AKT、m TOR磷酸化蛋白表达均明显上调(P<0.01,P<0.01),(P<0.01,P<0.01)。结论慢性孕前应激可诱导Balb/c母鼠表现出产后抑郁样症状,其发病机制可能与下调海马AKT/m TOR信号通路的蛋白表达有关。在此产后抑郁模型上,中药越甘具有与西药氯胺酮一致的快速抗抑郁作用,其作用机制可能与上调AKT/m TOR信号通路有关。 相似文献
2.
《中国药理学通报》2016,(7)
目的观察越鞠甘麦大枣汤对子代抑郁症的快速疗效,并分析其对Akt及m TOR分子的影响。方法成功建立产后抑郁子代模型后,随机分组如下:正常子代组(CTL-F1,8只),抑郁子代生理盐水组(Veh,8只)、越鞠甘麦大枣汤组(YG,8只)。Veh组给予生理盐水,YG组给予越鞠甘麦大枣汤(8.3 g·kg~(-1))。单次给药24 h后测量强迫游泳实验(FST)。取脑,Western blot法检测小鼠海马Akt及m-TOR的磷酸化及总体水平。结果 YG组的游泳不动时间比Veh组明显缩短(P<0.01),并且小鼠海马p-Akt和p-m TOR表达明显上调(P<0.05)。结论越鞠甘麦大枣汤可能通过上调Akt和m TOR表达,快速缓解子代抑郁样行为。 相似文献
3.
张书瑶 《中国现代药物应用》2021,(1):211-213
目的 分析甘麦大枣汤对脑梗死病后焦虑抑郁及神经功能的影响.方法 70例脑梗死患者,以随机抽签的方式分为对照组和观察组,各35例.对照组以盐酸帕罗西汀治疗,观察组在对照组的基础上加用甘麦大枣汤治疗.比较两组患者的焦虑自评量表(SAS)、抑郁自评量表(SDS)、美国国立卫生研究院卒中量表(NIHSS)、日常生活能力量表(A... 相似文献
4.
目的 探讨更年期抑郁患者临床治疗中同时服用甘麦大枣汤和益坤饮的效果。方法 从河源市中医院2020年4月至2021年5月收治的更年期抑郁患者中选取78例,通过随机数表法分为两组。对照组(39例)患者口服益坤饮汤剂进行治疗,观察组(39例)患者同时口服益坤饮汤剂和甘麦大枣汤进行治疗。观察两组服药治疗2个月后抑郁[抑郁自评量表(SDS)评分]、更年期症状(Kupperman评分)、激素水平[促黄体生成素(LH)、雌二醇(E2)等]及睡眠质量[总睡眠时间(TST)、睡眠潜伏期(SL)等]的变化情况。结果治疗后观察组SDS及Kupperman评分均低于对照组,差异有统计学意义(t=4.279、11.503,均P <0.05);观察组治疗后FSH、LH水平均低于对照组,E2水平高于对照组,差异有统计学意义(t=8.264、8.671、3.257,均P<0.05);治疗后观察组TST、SE大于对照组,SL、AT、AWT则小于对照组,差异有统计学意义(t=13.068、8.322、27.074、7.894、24.417,均P <0.05)。... 相似文献
5.
目的探讨加味越鞠汤口服对糖尿病前期患者血糖、血脂及肥胖指标的影响情况。方法选择本院2016年1月~2017年1月收治的86例气滞痰阻证糖尿病前期患者进行研究,将其随机分为实验组和对照组每组43例,两组均接受饮食、生活、日常锻炼等糖尿病基础干预治疗,实验组在此基础上接受加味越鞠汤口服治疗,治疗3个月后,对两组患者的血糖指标、血脂指标以及肥胖指标进行比较。结果经过治疗,实验组FBG、2h PG以及Hb A1C较对照组下降更加明显(P<0.05);LDL-C、TG、TC改善程度较对照组更加明显(P<0.05);BMI、WC以及WHR下降程度均较对照组更加明显(P<0.05)。结论加味越鞠汤能够显著降低糖尿病前期患者血糖水平,改善血脂水平以及肥胖状况,适合在临床上推广使用。 相似文献
6.
7.
8.
《中国药理学通报》2019,(2)
目的探讨越鞠丸对慢性皮质酮诱导小鼠的抑郁样行为及神经新生的作用。方法 C57BL/6N小鼠进行皮质酮注射造模及给药,行为学检测模型及药效,免疫组化法比较小鼠海马DG区Ki67~+细胞数量,蛋白免疫印迹法检测PKA-ERK-CREB信号通路的表达变化。结果糖水偏好结果显示,皮质酮诱导小鼠糖水偏好程度明显下降,越鞠丸则能逆转这一表型;悬尾测试和陌生环境摄食测试的结果与糖水偏好结果相类似。免疫组化结果显示,皮质酮诱导小鼠海马DG区Ki67~+细胞数量明显减少,而越鞠丸能够增加阳性细胞数量。蛋白免疫印迹结果显示,皮质酮诱导小鼠海马中PKA、CREB、ERK的表达水平均明显下调,而越鞠丸则可以上调这些蛋白表达。结论在皮质酮诱导抑郁模型小鼠中,越鞠丸通过激活PKA-ERK-CREB信号通路,进而增强海马神经新生,从而起到抗抑郁的作用。 相似文献
9.
《中国药房》2017,(13):1758-1762
目的:考察绿萼梅总黄酮对慢性应激抑郁模型大鼠抑郁行为的影响及机制。方法:将60只大鼠随机分为生理盐水组、模型组、氟西汀组(阳性对照,20 mg/kg)和绿萼梅总黄酮低、中、高剂量组(80、160、240 mg/kg),每组10只。除生理盐水组外,其余各组大鼠均采用慢性不可预见性温和应激(CUMS)+孤养法复制抑郁模型,并于造模同时ig相应药物,每天1次,连续28 d。观察大鼠体质量、摄食量的变化及糖水偏爱程度;通过强迫游泳实验、悬尾实验测定大鼠不动时间以及旷场实验测定大鼠中央格停留时间、水平穿越格数、站立次数、修饰次数的变化;并测定末次给药24 h后大鼠血清中肿瘤坏死因子α(TNF-α)、皮质醇、白细胞介素6(IL-6)、5-羟色胺(5-HT)水平。结果:与生理盐水组比较,模型组大鼠的体质量增加值、摄食量、糖水偏爱百分比均降低;强迫游泳和悬尾实验的不动时间延长;旷场实验的中央格停留时间延长、水平穿越格数、站立次数、修饰次数均减少;血清中TNF-α、皮质醇水平升高,IL-6、5-HT水平降低,差异均有统计学意义(P<0.05或P<0.01)。与模型组比较,除绿萼梅总黄酮低剂量组大鼠糖水偏爱百分比、强迫游泳不动时间、旷场实验修饰次数以及绿萼梅总黄酮低、中剂量组大鼠血清中IL-6、5-HT水平改善不明显外,其余各给药组大鼠上述指标均明显改善(P<0.05或P<0.01)。结论:绿萼梅总黄酮能明显改善CUMS诱导的大鼠抑郁行为,其机制可能与抑制炎症反应、调节下丘脑-垂体-肾上腺轴功能有关。 相似文献
10.
目的:探讨解郁汤的抗抑郁作用及可能机制。方法:以慢性轻度不可预见性应激方法建立小鼠抑郁症模型,以糖水消耗、悬尾实验、强迫游泳实验、开野实验进行行为学评分,并通过UPLC—T—QMS系统检测其脑内单胺类神经递质的含量,观察模型小鼠给药前后的变化。通过免疫组化检测小鼠海马区BDNF以及5-Brdu表达。结果:与空白组相比.模型组的小鼠蔗糖水消耗量明显下降,强迫游泳不动时间、悬尾不动时间均显著增加,交叉次数、直立次数显著减少,脑内的去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量降低(P〈0.05)。与模型组相比,解郁汤组小鼠蔗糖水消耗量显著升高,强迫游泳不动时间、悬尾不动时间均显著减少(P〈0.05)。解郁汤能显著增加大鼠脑内去甲肾上腺素、5-羟色胺、5-羟色胺吲哚乙酸含量(P〈0.05)。解郁汤能增加小鼠脑内海马区BDNF以及5-Brdu表达。结论:解郁汤具有抗抑郁作用,其作用机制可能与调节中枢单胺类神经递质的调节以及促进海马神经元再生有关。 相似文献
11.
Comments on an animal model of depression 总被引:1,自引:0,他引:1
Depression is a multifactorial illness and genetic factors play a role in its etiology. The understanding of its pathophysiology relies on the availability of experimental models potentially mimicking the disease. Here is presented a model built up by selective breeding of mice with strikingly different responses in the tail suspension test, a stress paradigm aimed at screening potential antidepressants. Indeed, "helpless" mice are essentially immobile in the tail suspension test, as well as the Porsolt forced-swim test, and they show reduced consumption of a palatable 2% sucrose solution. In addition, helpless mice exhibit sleep-wakefulness alterations resembling those classically observed in depressed patients, notably a lighter and more fragmented sleep, with an increase pressure of rapid eye movement sleep. Compared with "nonhelpless" mice, they display higher basal serum corticosterone levels and lower serotonin metabolism index in the hippocampus. Remarkably, serotonin1A autoreceptor stimulation induced greatest hypothermia and inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis in helpless than in nonhelpless mice. Thus, helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans. Finally, both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine. The helpless line of mice may provide an opportunity to approach genes influencing susceptibility to depression and to investigate neurophysiological and neurochemical substrates underlying antidepressant effects. 相似文献
12.
Sheldon H. Preskorn Thomas A. Kent Robin K. Glotzbach George H. Irwin Jay V. Solnick 《Psychopharmacology》1984,84(2):196-199
In the tetrabenazine (TBZ) model of depression, the cerebromicrocirculation was discovered to respond abnormally to metabolic demand as mimicked by the administration of CO2. Altered responsivity of cerebral blood flow and effective permeability of the blood — brain barrier to changes in PaCO2 were found. These physiologic defects coincided temporally with TBZ-induced depletion of central norepinephrine and dopamine and with the development of the behavioral effects of TBZ (the end points used to test the antidepressant potential of experimental drugs). Pretreatment with amitriptyline (a standard antidepressant and amine reuptake inhibitor) prevented the development of these TBZ-induced abnormalities in the cerebromicrocirculation, just as it prevented the behavioral effects. 相似文献
13.
《European neuropsychopharmacology》2010,20(11):802-812
Mood disorders are highly prevalent and often difficult to treat. One of the most important obstacles in research on depression is the limited availability of reliable and valid animal models. Here we demonstrate that the exposure of mice to artificial daylight for 22 h per day produces a spectrum of behavioral and endocrine symptoms reminiscent to those seen in animal models of depression. Oral administration of the antidepressant imipramine has strong impact on these symptoms. Our results indicate that long-light exposure of mice represents a simple new method to study depression. 相似文献
14.
A neuropharmacologically-relevant animal model of depression 总被引:5,自引:0,他引:5
The phenomenon of “learned helplessness” was evaluated as a potential animal model of depression. Imipramine, but not chlorpromazine or lorazepam, had a delayed protective effect on the development of this behavior although lorazepam was effective after a single dose. Dose-response curves related either to concentration of imipramine in drinking water or to free drug levels in brain were linear with higher drug levels associated with a lowered degree of learned helplessness following chronic administration. The effects of imipramine on the development of learned helplessness were seen following four days of access to drug in drinking water, but not after 1, 2 or 3 days. This model, although clearly not a perfect fit with depression in humans, has many characteristics which suggest its utility in further studies of the mechanism of action of antidepressants. 相似文献
15.
Ashwini V. Karve Sagar S. Jagtiani Kunal A. Chitnis 《Indian journal of pharmacology》2013,45(3):244-247
Objective:
To evaluate the effects of allopurinol and febuxostat on depression using Forced Swim Test (FST) in mice.Materials and Methods:
Allopurinol (39 mg/kg p. o) and febuxostat (15.6 mg/kg p. o) were administered once daily for 21 successive days to Swiss Albino mice. On the 21st day, the effect of the drug on locomotion was tested using photo-actometer followed by the recording of immobility period in the FST and the results were compared with the standard drug fluoxetine (10 mg/kg p. o).Results:
Allopurinol and febuxostat expressed significant antidepressant like effect as indicated by reduction in the immobility period of mice in the FST as compared to control group. The effects of allopurinol and febuxostat were found to be comparable to that of fluoxetine.Conclusion:
The results of the present study indicate that allopurinol and febuxostat possess significant antidepressant like activity.KEY WORDS: Forced swim test, photo-actometer, serotonin, tryptophan 相似文献16.
Rats working on a food-reinforced operant schedule and exhibiting behavioral depression following administration of D,L-5-hydroxytryptophan (5-HTP) were pretreated with one of three drugs: methysergide, fluoxetine, or amitriptyline. The former two drugs were used to establish a basis for distinguishing between pre- and postsynaptic events. We found that methysergide, a known postsynaptic blocker of serotonin, almost completely abolished the depressive effect of 5-HTP, whereas fluoxetine, a known specific uptake blocker of serotonin, potentiated the depressive effect of the 5-hydroxytryptamine (5-HT) precursor. Amitriptyline, one of the commonly prescribed antidepressive drugs, reduced the behavioral depression following 5-HTP by approximately 50%. These data indicate that amitriptyline can act as an antagonist of 5-HT at the postsynaptic receptor. The results of this study, as well as those recently reported from CNS membrane binding studies, suggest that the therapeutic effects of some antidepressive drugs may be explained by their postsynaptic rather than presynaptic properties at central serotonergic receptors. Thus, these studies support the hypothesis that some types of human depression may be primarily due to an excess of free 5-HT acting at postsynaptic receptors. 相似文献
17.
Rationale Anhedonia is a core symptom of major depression. Deficits in reward function, which underlie anhedonia, can be readily assessed
in animals. Therefore, anhedonia may serve as an endophenotype for understanding the neural circuitry and molecular pathways
underlying depression.
Objective Surprisingly, there is scant knowledge regarding alterations in brain reward function after olfactory bulbectomy (OB), an
animal model which results in a behavioural syndrome responsive to chronic antidepressant treatment. Therefore, the present
studies aimed to assess reward function after bulbectomy.
Materials and methods The present study utilized sucrose preference, cocaine-induced hyperlocomotion and intra-cranial self-stimulation (ICSS) responding
to examine reward processes in the OB model.
Results Bulbectomized animals showed a marked preference (>90%) for 0.8% sucrose solution compared with water; similar to the preference
exhibited by sham controls. Importantly, there were pronounced deficits in brain reward function, as assessed using ICSS,
which lasted 8 days before returning to baseline levels. Furthermore, bulbectomized animals were hyper-responsive to the locomotor
stimulating properties of an acute and a repeated cocaine regimen. However, no difference in ICSS facilitation was observed
in response to an acute cocaine injection.
Conclusions Taken together, these results suggest that bulbectomized rats display alterations in brain reward function, but these changes
are not long-lasting and thus, not amenable to investigating the effects of pharmacological interventions. However, given
that OB animals are hypersensitive to drugs of abuse, bulbectomy may be an appropriate inducing factor for the development
of animal models of co-morbid depression and drug dependence. 相似文献
18.
Tizabi Y Overstreet DH Rezvani AH Louis VA Clark E Janowsky DS Kling MA 《Psychopharmacology》1999,142(2):193-199
Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals
with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an
attempt at self-medication with nicotine by these individuals. Although some animal and human studies suggest that nicotine
may act as an antidepressant, further verification of this hypothesis and involvement of nicotinic cholinergic system in depressive
symptoms is required. Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression. These rats,
selectively bred for their hyperresponsiveness to cholinergic stimulation, show an exaggerated immobility in the forced swim
test compared to their control Flinders Resistant Line (FRL) rats. Acute or chronic (14 days) administration of nicotine (0.4 mg/kg
SC) significantly improved the performance of the FSL but not the FRL rats in the swim test. The effects of nicotine on swim
test were dissociable from its effects on locomotor activity. Moreover, the FSL rats had significantly higher [3H]cytisine binding (selective for the α4β2 nicotinic receptor subtype) but not [125I]alpha-bungarotoxin binding (selective for the α7 subtype) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the
involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists
may have therapeutic benefits in depressive disorders.
Received: 9 June 1998/Final version: 6 August 1998 相似文献
19.
《Pharmaceutical biology》2013,51(5):533-538
AbstractContext: It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model.Objective: This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST).Materials and methods: Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60?mg/kg in male Wistar rats. Insulin (4?IU/kg) plus CNZ acute i.p. treatment (0.25?mg/kg) was administered 24, 5 and 1?h before the FST. Nondiabetic control rats received i.p. injections of saline (1?mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined.Results: Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04?±?0.55), while the activity of catalase (51.83?±?19.02) and SOD (2.30?±?1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15?±?0.02) in the liver of the animals was decreased.Discussion and conclusion: Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST. 相似文献
20.
《European journal of pharmacology》1999,364(2-3):123-132
The limitations of antidepressant drugs to treat depression has warranted ongoing research to identify pharmacological agents and strategies which offer a faster onset of action and greater therapeutic efficacy. Noradrenaline and serotonin are widely reported to be involved in the mechanism of action of antidepressants and the recent development of selective reuptake inhibitors of these transmitters has provided the opportunity to determine the effects of targeting these transmitter systems, alone and in combination, in an antidepressant response. The present study investigated the effects of reboxetine, a new antidepressant that selectively inhibits noradrenaline reuptake, sertraline, a selective serotonin reuptake inhibitor and a combination treatment composed of the two drugs in the olfactory bulbectomized (OB) rat model of depression. Sub-acute (2 days) administration of reboxetine (2.5, 5, and 10 mg/kg, i.p.) to sham-operated and OB rats reduced the immobility time in the forced swim test. Repeated (14 days) reboxetine (10 mg/kg) treatment attenuated the OB-related behavioural hyperactivity in the `open-field' test. Examination of the onset of the antidepressant effect in the `open-field' test demonstrated that reboxetine (10 mg/kg), sertraline (5 mg/kg) and the combination reduced the behavioural hyperactivity after 14 days but not before this following 3, 7 or 10 days of treatment. Reduced 5-hydroxyindoleacetic acid (5-HIAA) concentrations in amygdaloid cortex of both sham and OB rats following sertraline and combination treatments are likely to be related to acute pharmacological effects on the reuptake of 5-hydroxytryptamine (5-HT). Attenuation of the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.05 mg/kg s.c.) and clonidine (0.1 mg/kg s.c.) occurred in the reboxetine and sertraline combination treated groups following both 7 and 14 days administration indicating changes to 5-HT1A receptor and α2-adrenoceptor sensitivity. The results indicate that changes to 8-OH-DPAT and clonidine-induced responses occur quicker with the combination treatment than with either reboxetine or sertraline treatments alone. 相似文献