Standardised ginseng extract G115® potentiates the antidepressant-like properties of fluoxetine in the forced swim test

2021 ◽  
pp. 1-7
Author(s):  
Dylan J. Terstege ◽  
Debra S. MacDonald ◽  
R. Andrew Tasker
Keyword(s):  
Prefrontal Cortex ◽  
Forced Swim Test ◽  
Ginseng Root ◽  
Group Differences ◽  
Post Mortem ◽  
Ginseng Extract ◽  
Significant Group ◽  
Swim Test ◽  
Forced Swim ◽  
Plus Maze

Abstract Objective: Ginsenosides, biologically active components of the root of Panax ginseng, have been reported to have therapeutic benefits in a number of disease states including psychiatric conditions such as major depressive disorder. Our objective was to determine if a standardised commercial ginseng extract, G115®, could reduce the signs of behavioural despair commonly observed in animal models of depression either alone or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. Methods: Male Sprague-Dawley (SD) rats (N = 51) were divided into four groups: vehicle control, G115® ginseng root extract, fluoxetine and fluoxetine plus G115®. Rats were trained to voluntarily consume treatments twice daily for 14 days and were then tested in an open field (OF), elevated plus maze (EPM) and forced swim test (FST). Post-mortem hippocampal and prefrontal cortex tissue was analysed for expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) by western blot. Results: One-way Analysis of Variance revealed no significant group differences in the OF or plus-maze performance on any variable examined. In the FST, fluoxetine significantly reduced immobility time and increased latency to immobility. The effects of fluoxetine were further significantly potentiated by co-administration of G115®. Post-mortem tissue analysis revealed significant group differences in BDNF expression in the left hippocampus and left prefrontal cortex without any accompanying changes in TrkB expression. Conclusions: We conclude that oral G115® significantly potentiates the antidepressant-like effect of fluoxetine in the FST in the absence of potentially confounding effects on locomotion and anxiety.

scholarly journals Effect of Passiflora Edulis Sims onReserpine Induced Fibromyalgia

2019 ◽  
Vol 12 (04) ◽  
pp. 2157-2165
Author(s):  
Naveen Sharma ◽  
Ajay Sharma ◽  
Vipin Kumar Sharma
Keyword(s):  
Forced Swim Test ◽  
Control Group ◽  
Tail Flick ◽  
Plant Leaves ◽  
Passiflora Edulis ◽  
Swim Test ◽  
Forced Swim ◽  
Plus Maze ◽  
Immobility Time ◽  
Passiflora Edulis Sims

This study was carried out to assess the possible effect of Passiflora edulis Sims on reserpine-induced fibromyalgia with using different animal models and commonly used in the Virginia, southern Illinois, southeast Kansas and India as a folk medicine. Possible effect of extract of the plant was evaluated on reserpine-induced fibromyalgia. For evaluating the effect of this Plant leaves extract, different models were used such as tail flick, radiant heat, hot plate and inclined plane model. Evaluation of anti-depression activity, forced swim test and elevated plus maze (EPM) model were used. Investigations were shown that reserpine-treated animals responded with significantly increased sensitivity of pain in tail flick latency, decreased threshold of paw-withdrawal and immobility time and in Randall test. Whereas Plant leaves extract at different level of doses (e.g. 200 and 400 mg/kg) has shown a significant reduction in time of immobility, withdrawal latency of tail and the significant increase in mechanical and thermal hyperalgesia. The Passiflora edulis Sims showed inhibition of algesic condition in all the models which was dose dependent. During forced swim test extract of plant showed the significant reduce immobility time as compared with the control group, also in the plus‐maze method, Plant leaves extract showed increased time spend in open arm. The results were confirmed that the use of the extract of leaves of Passiflora edulis Sims in the traditional management of pain and enhances behavioural activity.

scholarly journals Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim Test

2017 ◽  
Vol 1 ◽  
pp. 247054701771298 ◽  
Author(s):  
Kaziya M Lee ◽  
Michal A Coelho ◽  
Kimberly R Sern ◽  
MacKayla A Class ◽  
Mark D Bocz ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Protein Expression ◽  
Effective Dose ◽  
Alcohol Withdrawal ◽  
Forced Swim Test ◽  
Drug Effects ◽  
Brain Regions ◽  
Significant Group ◽  
Swim Test ◽  
Forced Swim

Traditionally, a reduction in floating behavior or immobility in the Porsolt forced swim test is employed as a predictor of anti-depressant efficacy. However, over the past several years, our studies of alcohol withdrawal-induced negative affect consistently indicate the coincidence of increased anxiety-related behaviors on various behavioral tests with reduced immobility in the forced swim test. Further, this behavioral profile correlates with increased mGlu5 protein expression within limbic brain regions. As the role for mGlu5 in anxiety is well established, we hypothesized that the reduced immobility exhibited by alcohol-withdrawn mice when tested in the forced swim test might reflect anxiety, possibly a hyper-reactivity to the acute swim stressor. Herein, we evaluated whether or not the decreased forced swim test immobility during alcohol withdrawal responds to systemic treatment with a behaviorally effective dose of the prototypical anxiolytic, buspirone (5 mg/kg). We also determined the functional relevance of the withdrawal-induced increase in mGlu5 expression for forced swim test behavior by comparing the effects of buspirone to a behaviorally effective dose of the mGlu5 negative allosteric modulator MTEP (3 mg/kg). Adult male C57BL/6J mice were subjected to a 14-day, multi-bottle, binge-drinking protocol that elicits hyper-anxiety and increases glutamate-related protein expression during early withdrawal. Control animals received only water. At 24-h withdrawal, animals from each drinking condition were subdivided into groups and treated with an intraperitoneal injection of buspirone, MTEP, or vehicle, 30 min prior to the forced swim test. Drug effects on general locomotor activity were also assessed. As we reported previously, alcohol-withdrawn animals exhibited significantly reduced immobility in the forced swim test compared to water controls. Both buspirone and MTEP significantly increased immobility in alcohol-withdrawn animals, with a modest increase also seen in water controls. No significant group differences were observed for locomotor activity, indicating that neither anxiolytic was sedating. These results provide predictive validity for increased swimming/reduced immobility in the forced swim test as a model of anxiety and provide novel evidence in favor of mGlu5 inhibition as an effective therapeutic strategy for treating hyper-anxiety during alcohol withdrawal.

scholarly journals Effect of lethal yellow (AY) mutation and photoperiod alterations on mouse behavior

2019 ◽  
Vol 23 (1) ◽  
pp. 55-61
Author(s):  
E. Y. Bazhenova ◽  
D. V. Fursenko ◽  
N. V. Khotskin ◽  
I. E. Sorokin ◽  
A. V. Kulikov
Keyword(s):  
Open Field ◽  
Home Cage ◽  
Elevated Plus Maze ◽  
Open Field Test ◽  
Forced Swim Test ◽  
Swim Test ◽  
Forced Swim ◽  
Plus Maze ◽  
Immobility Time ◽  
Lethal Yellow

Decrease in natural illumination in fall/winter months causes depressive-like seasonal affective disorders in vulnerable individuals. Obesity is another risk factor of depression. The lethal yellow (AY) mutation causes ectopic expression of agouti protein in the brain. Mice heterozygous for AY mutation (AY/a) are obese compared to their wild-type littermates (a/a). The main aims of the study were to investigate the effects of AY mutation, photoperiod and the interaction between these factors on daily activity dynamics, feeding, locomotor and exploratory activities, anxiety-related and depressive-like behaviors in mild stress condition. Six weeks old mouse males of AY/a and a/a lines were divided into four groups eight animals each and exposed to long- (14 h light and 10 h darkness) or short- (4 h light and 20 h darkness) day conditions for 28 days. Then the behavior of these mice was successively investigated in the home cage, open field, elevated plus-maze and forced swim tests. We did not observed any effect of AY mutation on the general activity, water and food consumption in the home cage; locomotion and exploration in the open field test; anxiety-related behavior in the open field and elevated plus-maze tests. At the same time, AY mutation increased depressive-like immobility time in the forced swim test (F1.28 = 20.03, p = 0.00012). Shortday conditions decreased nocturnal activity in the home cage, as well as locomotion (F1.28 = 16.33, p = 0.0004) and exploration (F1.28 = 16.24, p < 0.0004) in the open field test. Moreover, short-day exposition decreased time spent in the center of the open field (F1.28 = 6.57, p = 0.016) and in the open arms of the elevated plus-maze (F1.28 = 12.08, p = 0.0017) tests and increased immobility time in the forced swim test (F1.28 = 9.95, p = 0.0038). However, no effect of the interaction between AY mutation and photoperiod on immobility time in the forced swim test was observed. Therefore, short-day photoperiod and AY mutation increased depressive-like behavior in the forced swim test by means of different mechanisms.

Individual differences in the elevated plus-maze and the forced swim test

2011 ◽  
Vol 86 (1) ◽  
pp. 46-51 ◽  
Author(s):  
Celio Estanislau ◽  
Anna Carolina Ramos ◽  
Paula Daniele Ferraresi ◽  
Naiara Fernanda Costa ◽  
Heloisa Maria Cotta Pires de Carvalho ◽  
...  
Keyword(s):  
Individual Differences ◽  
Elevated Plus Maze ◽  
Forced Swim Test ◽  
Swim Test ◽  
Forced Swim ◽  
Plus Maze

Diazepam normalizes anxiety in rats with experimental anxiety-depressive state induced by diprotin A in the first postnatal week

2018 ◽  
pp. 5-12
Author(s):  
Н.А. Крупина ◽  
Н.Н. Хлебникова
Keyword(s):  
Elevated Plus Maze ◽  
Forced Swim Test ◽  
Depressive State ◽  
New Model ◽  
Serum Corticosterone ◽  
Swim Test ◽  
Elevated Plus Maze Test ◽  
Maze Test ◽  
Forced Swim ◽  
Plus Maze

В предыдущих исследованиях мы показали, что у крысят, подвергнутых на второй-третьей неделях постнатального развития действию ингибиторов дипептидилпептидазы IV (ДП-IV), в дальнейшем развивалось смешанное тревожно-депрессивное состояние, которое характеризовалось повышением уровня кортикостерона в сыворотке крови. Трициклический антидепрессант имипрамин купировал проявления депрессивноподобного поведения у таких крыс в тесте принудительного плавания. Данные свидетельствовали в пользу соответствия данных моделей основным критериям валидности - «внешней схожести», прогностическому и конструкционному критериям. Недавно в наших исследованиях была разработана новая модель смешанного тревожно-депрессивного состояния, индуцируемая действием ингибитора ДП-IV дипротина А в первую неделю постнатального развития крысят. Цель настоящего исследования - валидизация данной модели тревожно-депрессивного состояния. Методы. Крысятам опытной группы вводили дипротин А (2 мг/кг, внутрибрюшинно), животным контрольной группы - физиологический раствор. У крыс подросткового возраста и взрослых животных оценивали двигательную активность (тест «Автоматизированное открытое поле»), уровень тревожности (тест «Приподнятый крестообразный лабиринт») и депрессивно-подобное поведение (тест принудительного плавания). Двухмесячным животным однократно вводили анксиолитик диазепам (1,25 мг/кг) с последующей оценкой уровня тревожности. Уровень кортикостерона в сыворотке крови определяли методом твердофазного иммуноферментного анализа. Результаты. Действие дипротина А индуцировало развитие депрессивноподобного поведения у крыс в возрасте 1 и 2 мес., и повышало уровень тревожности у двухмесячных крыс. Содержание кортикостерона в крови таких животных превышало контрольный уровень. Диазепам нормализовал уровень тревожности и привыкание в тесте «Приподнятый крестообразный лабиринт». Заключение. Полученные данные свидетельствуют в пользу валидности новой модели смешанного тревожно-депрессивного состояния у крыс, создаваемой действием ингибитора ДП-IV дипротина А в первую неделю постнатального развития. Earlier we have shown that rat pups treated with dipeptidyl peptidase IV (DP-IV) inhibitors in the second to third postnatal weeks further developed a mixed anxiety-depressive state, which was characterized by increased blood corticosterone. Imipramine, a tricyclic antidepressant, suppressed the depressive-like behavior in such rats in the forced swim test. This supported the consistency of these models with the main criteria of validity, «outward similarity» and predictive and construction criteria. Recently we have developed a new model of mixed anxiety-depressive state, induced by a DP-IV inhibitor, diprotin A, administered in the first postnatal week. The aim of this study was to validate this model of anxiety-depressive state. Methods. Diprotin A (2 mg/kg, i.p.) was administered to rats of the experimental group, and saline - to the control animals. Motor activity (automated open field test), anxiety (elevated plus-maze test), and depressive-like behavior (forced swim test) were evaluated in adolescent and adult rats. Two-month-old animals were injected with a single dose of the anxiolytic diazepam (1.25 mg/kg) followed by the anxiety tests. Serum corticosterone level was measured using enzyme immunoassay. Results. Diprotin A induced depressive-like behavior in rats aged one and two months and increased anxiety in two-month-old rats. In these animals, serum corticosterone concentration exceeded the control level. Diazepam normalized anxiety and habituation in the elevated plus-maze test. Conclusion. The study supported the validity of the new model of mixed anxiety-depressive state in rats induced by the DP-IV inhibitor, diprotin A, administered in the first postnatal week.

scholarly journals Ribosomal protein S6 kinase 1 signaling in prefrontal cortex controls depressive behavior

2015 ◽  
Vol 112 (19) ◽  
pp. 6188-6193 ◽  
Author(s):  
Jason M. Dwyer ◽  
Jaime G. Maldonado-Avilés ◽  
Ashley E. Lepack ◽  
Ralph J. DiLeone ◽  
Ronald S. Duman
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Forced Swim Test ◽  
Critical Role ◽  
Dominant Negative ◽  
Synaptic Proteins ◽  
S6 Kinase ◽  
Swim Test ◽  
Forced Swim ◽  
Number Of Patients

Current treatments for major depressive disorder (MDD) have a time lag and are ineffective for a large number of patients. Development of novel pharmacological therapies requires a comprehensive understanding of the molecular events that contribute to MDD pathophysiology. Recent evidence points toward aberrant activity of synaptic proteins as a critical contributing factor. In the present studies, we used viral-mediated gene transfer to target a key mediator of activity-dependent synaptic protein synthesis downstream of mechanistic target of rapamycin complex 1 (mTORC1) known as p70 S6 kinase 1 (S6K1). Targeted delivery of two mutants of S6K1, constitutively active or dominant-negative, to the medial prefrontal cortex (mPFC) of rats allowed control of the mTORC1/S6K1 translational pathway. Our results demonstrate that increased expression of S6K1 in the mPFC produces antidepressant effects in the forced swim test without altering locomotor activity. Moreover, expression of active S6K1 in the mPFC blocked the anhedonia caused by chronic stress, resulting in a state of stress resilience. This antidepressant response was associated with increased neuronal complexity caused by enhanced S6K1 activity. Conversely, expression of dominant-negative S6K1 in the mPFC resulted in prodepressive behavior in the forced swim test and was sufficient to cause anhedonia in the absence of chronic stress exposure. Together, these data demonstrate a critical role for S6K1 activity in depressive behaviors, and suggest that pathways downstream of mTORC1 may underlie the pathophysiology and treatment of MDD.

scholarly journals The antidepressant effects of asperosaponin VI are mediated by the suppression of microglial activation and reduction of TLR4/NF-ĸB induced IDO expression

2020 ◽  
Author(s):  
Jinqiang Zhang ◽  
Saini Yi ◽  
Yahui Li ◽  
Chenghong Xiao ◽  
Chan Liu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Signaling Pathway ◽  
Microglial Activation ◽  
Forced Swim Test ◽  
Kynurenine Pathway ◽  
Antidepressant Effect ◽  
Dependent Manner ◽  
Swim Test ◽  
Forced Swim ◽  
Glutamate Transmission

AbstractAimIndoleamine 2, 3-dioxygenase (IDO) is responsible for the progression of the kynurenine pathway, which has been implicated in the pathophysiology of inflammation-induced depression. It has been reported that asperosaponin VI (ASA VI) could play a neuroprotective role through anti-inflammatory and antioxidant. In this study, we examined the antidepressant effect of ASA VI in LPS-treated mice and further explored its molecular mechanism by insight into the microglial kynurenine pathway.MethodsTo produce the model, lipopolysaccharide (LPS) (0.83 mg/kg) was administered intraperitoneally to mice. The mice received ASA VI (10 mg/kg, 20mg/kg, 40mg/kg and 80mg/kg, i.p.) thirty minutes prior to LPS injection. Depressive-like behaviors were evaluated based on the duration of immobility in the forced swim test. Microglial activation and inflammatory cytokines were detected by immunohistochemistry, real-time PCR and ELISA. The TLR4/NF-ĸB signaling pathway and the expression of IDO, GluA2, and CamKIIβ were measured by western blotting.ResultsASA VI demonstrated significant antidepressant activity in the presence of LPS on immobility and latency times in the forced swim test. The LPS-induced activation of microglia and inflammatory response were inhabited by ASA VI in a dose-dependent manner. TLR4/NF-κB signaling pathway also was suppressed by ASA VI in the hippocampus and prefrontal cortex of LPS-treated mice. Furthermore, ASA VI inhibited the increase in IDO protein expression and normalized the aberrant glutamate transmission in the hippocampus and prefrontal cortex as a result of LPS administration.ConclusionOur results propose a promising antidepressant effect for ASA VI possibly through the downregulation of IDO expression and normalization of the aberrant glutamate transmission. This remedying effect of ASA VI could be attributed to suppress microglia-mediated neuroinflammatory response via inhibiting the TLR4/NF-κB signaling pathway.

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