Effects of Unpredictable Chronic Mild Stress on the Effects of Antidepressants in the Forced Swimming Test

We investigate the antidepressant-like effect and mechanism of electroacupuncture (EA) on a chronic unpredictable mild stress rats depression-like behavior. In our study, depression in rats was induced by unpredictable chronic mild stress (UCMS) and isolation for four weeks. Male Sprague-Dawley rats were randomly divided into four groups: Normal, Model, EA, and Sham EA. EA treatment was administered for two weeks, once a day for five days a week. Two acupoints, Yintang (EX-HN3) and Baihui (GV20), were selected. For sham EA, acupuncture needles were inserted shallowly into the acupoints: EX-HN3 and GV20. No electrostimulator was connected. The antidepressant-like effect of the electroacupuncture treatment was measured by sucrose intake test, open field test, and forced swimming test in rats. The protein levels of phosphorylated extracellular regulated protein kinases (p-ERK1/2)/ERK1/2 and p-P38/P38 in the hippocampus (HP) were examined by Western blot analysis. Our data demonstrate that EA treatment decreased the immobility time of forced swimming test and improved the sucrose solution intake in comparison to unpredictable chronic mild stress and placebo sham control. Electroacupuncture may act on depression by enhancing p-ERK1/2 and p-p38 in the hippocampus.

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Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression

Progress in Neuro-Psychopharmacology and Biological Psychiatry ◽

10.1016/j.pnpbp.2009.07.020 ◽

2009 ◽

Vol 33 (8) ◽

pp. 1417-1424 ◽

Cited By ~ 139

Author(s):

Haixia Dang ◽

Ying Chen ◽

Xinmin Liu ◽

Qiong Wang ◽

Liwei Wang ◽

...

Keyword(s):

Forced Swimming Test ◽

Chronic Mild Stress ◽

Forced Swimming ◽

Mild Stress ◽

Antidepressant Effects ◽

Swimming Test ◽

Stress Models

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Using tests and models to assess antidepressant-like activity in rodents

Current Issues in Pharmacy and Medical Sciences ◽

10.1515/cipms-2016-0013 ◽

2016 ◽

Vol 29 (2) ◽

pp. 61-65 ◽

Cited By ~ 2

Author(s):

Ewa Kedzierska ◽

Izabela Wach

Keyword(s):

Animal Models ◽

Learned Helplessness ◽

Forced Swimming Test ◽

Chronic Mild Stress ◽

Tail Suspension Test ◽

Depression Treatment ◽

Mild Stress ◽

Animal Models Of Depression ◽

Important Challenge ◽

Swimming Test

Abstract In today's world, depression is one of the more prevalent forms of mental illness. According to WHO, about 10%-30% of all women and 7%-15% of all men are afflicted by depression at least once in their life-times. Today, depression is assessed to be affecting 350 million people. Regarding this issue, an important challenge for current psychopharmacology is to develop new, more effective pharmacotherapy and to understand the mechanism of action of known antidepressants. Furthermore, there is the necessity to improve the effectiveness of anti-depression treatment by way of bringing about an understanding of the neurobiology of this illness. In achieving these objectives, animal models of depression can be useful. Yet, presently, all available animal models of depression rely on two principles: the actions of known antidepressants or the responses to stress. In this paper, we present an overview of the most widely used animal tests and models that are employed in assessing antidepressant-like activity in rodents. These include amphetamine potentiation, reversal of reserpine action, the forced swimming test, the tail suspension test, learned helplessness, chronic mild stress and social defeat stress. Moreover, the advantages and major drawbacks of each model are also discussed.

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Experimental anxiety-depressive state in rats caused by neonatal exposure to the inhibitor of dipeptidyl peptidase IV, diprotin A: effects of imipramine

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/igpp.2017.4.8517 ◽

2017 ◽

pp. 4-12

Author(s):

Н.Н. Хлебникова ◽

Н.А. Крупина

Keyword(s):

Forced Swimming Test ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Forced Swimming ◽

Face Validity ◽

Neonatal Exposure ◽

Depressive State ◽

Serum Corticosterone ◽

Old Rats ◽

Swimming Test

В наших предыдущих исследованиях было показано, что ингибитор пролинспецифической пептидазы дипептидилпептидазы-IV (ДП-IV, EC 3.4.14.5) трипептид дипротин А, введенный крысам в 5-18 постнатальные дни, приводит к развитию у крыс подросткового возраста и взрослых животных эмоционально-мотивационных расстройств. Такие расстройства можно рассматривать как модель смешанного тревожно-депрессивного состояния. Однако специальных исследований по валидности данной модели проведено не было. Цель настоящей работы состояла в проверке влияния трициклического антидепрессанта имипрамина (ИМИ) на депрессивноподобное поведение крыс и уровень кортикостерона в сыворотке крови животных на модели смешанного тревожно-депрессивного состояния. Методика. У крыс в возрасте одного и двух мес. определяли уровень тревожности в автоматизированном тесте «Приподнятый крестообразный лабиринт» и оценивали депрессивноподобное поведение в тесте принудительного плавания. ИМИ вводили взрослым животным в течение 10 дней (20 мг/кг/день, интрагастрально). Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа. Результаты. Неонатальное действие дипротина А приводило к повышению тревожности у крыс в возрасте 1 мес. Депрессивноподобное поведение обнаружено у животных в возрасте одного и двух мес. ИМИ нормализовал поведение животных в тесте принудительного плавания и снижал уровень кортикостерона в сыворотке крови крыс. Кроме того, ИМИ снижал вес крыс. Заключение. Результаты исследования свидетельствуют в пользу адекватности модели смешанного тревожно-депрессивного расстройства, возникающего у крыс вследствие действия ингибитора ДП-IV дипротина А на второй-третьей неделях постнатального развития, клиническому прообразу заболевания по критериям «внешней схожести», прогностической и конструкционной валидности. Previously, we have shown that the inhibitor of proline-specific peptidase, dipeptidyl peptidase-IV (DP-IV, EC 3.4.14.5), tripeptide diproptin A administered on postnatal days 5-18 induced emotional and motivational disorders in adolescent and adult rats. These disorders can be considered a model of a mixed anxiety-depression-like disorder. However, validation studies of this model are not available. The aim of this work was to test the effect of the tricyclic antidepressant, imipramine (IMI), on depressive-like behavior in rats and the level of serum corticosterone using the model of mixed anxiety-depressive state. Methods. The level of anxiety was assessed by the automated Elevated Plus Maze test and the depressive-like behavior was evaluated by the forced swimming test in one- and two-month old rats. IMI was administered to adult animals for ten days (20 mg/kg a day, intragastrically). Serum corticosterone concentrations were measured using ELISA. Results. The neonatal exposure to diprotin A increased anxiety in one-month old rats. The depressive-like behavior was observed in animals aged one and two months. IMI normalized behavior of animals in the forced swimming test and reduced serum levels of corticosterone. Also, IMI reduced body weight of rats. Conclusion. The results of the study evidenced adequacy of the model of mixed anxiety-depressive state induced by the DP-IV inhibitor, diprotin A, on the second and third postnatal weeks to the clinical prototype of disease according to criteria of face validity, predictive and construct validity.

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Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

Pharmaceuticals ◽

10.3390/ph14070659 ◽

2021 ◽

Vol 14 (7) ◽

pp. 659

Author(s):

Juthamart Maneenet ◽

Orawan Monthakantirat ◽

Supawadee Daodee ◽

Chantana Boonyarat ◽

Yutthana Chotritthirong ◽

...

Keyword(s):

Mrna Expression ◽

Chronic Mild Stress ◽

Antidepressant Activity ◽

Piper Nigrum ◽

Psychiatric Disease ◽

Mild Stress ◽

Herbal Formula ◽

Necrosis Factor Alpha ◽

Unpredictable Chronic Mild Stress

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

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