Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength

2009 ◽  
Vol 98 (1-2) ◽  
pp. 67-72 ◽  
Author(s):  
Wendie Marks ◽  
Neil M. Fournier ◽  
Lisa E. Kalynchuk
2021 ◽  
pp. 026988112199688
Author(s):  
Eduardo R Butelman ◽  
Caroline Baynard ◽  
Bryan D McElroy ◽  
Thomas E Prisinzano ◽  
Mary Jeanne Kreek

Background: Novel short-acting κ(kappa)-opioid receptor selective antagonists are translational tools to examine the impact of the κ-receptor/dynorphin system in assays related to central nervous system dysfunction (e.g., substance use disorders, anhedonia and depression). The effects of such compounds have been compared in males and females under very limited conditions. Aims: The goal of this study was to examine potential sex differences in the effects of a κ-agonist and a short-acting κ-antagonist in an ethologically relevant test of anhedonia, the “splash test” of self-grooming, and also in the forced swim test and in locomotor activity. Methods: We examined the dose-dependence of grooming deficits caused by the κ-agonist U50,488 (0.1–3.2 mg/kg intraperitoneal (i.p.)) in gonadally intact adult male and female C57BL/6J mice. We then compared the effects of the short-acting κ-antagonist LY2795050 ((3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)); 0.032–0.1 mg/kg i.p.) in blocking grooming deficits caused by U50,488 (3.2 mg/kg). The effects of LY2795050 were also studied in the forced swim test (FST). The effects of LY2795050 in blocking the locomotor depressant effects of U50,488 (10 mg/kg) were also studied. Results: U50,488 produced dose-dependent grooming deficits in male and female mice, and LY2795050 prevented these effects. In contrast, LY2795050 decreased immobility in the FST in males at a dose of 0.1 mg/kg, but not in females, up to a dose of 0.32 mg/kg. Also, LY2795050 (0.32 mg/kg) prevented and also reversed the locomotor-depressant effects of U50,488 (10 mg/kg), in males and females. Conclusions: This study further implicates the κ-receptor system in ethologically relevant aspects of anhedonia, and confirms sexual dimorphism in some behavioral effects of novel κ-antagonists.


Author(s):  
K. Mohana Rao ◽  
Siva B. ◽  
Mahendra U. ◽  
Vinay K. ◽  
A. Narendra Babu ◽  
...  

Depression is a state of excessive sensitivity to criticism, fear of rejections, lack of self-interest, loss of pleasure. In the traditional systems of medicine, many plants and formulations have been used to treat depression for thousands of years. In recent times, research on the plants increased globally and so many plants provide the evidence to cure diseases. Ocimum sanctum, popularly known as Tulsi is one of the sacred herbs for Hindus in the Indian subcontinent. It has a versatile role in traditional medicine. The fruits of Piper nigrum are used to make black pepper. This hotly pungent spice is one of the earliest known and most widely used spices in the world today. Wide range of animal tests for antidepressant agents are commonly used. The Forced swim test and Tail suspension test in mice were mostly used. Hence in the present study Forced swim test was used as animal model of depression. In present study immobility time in Forced swim test was significantly decreased by a combination of Piper nigrum fruit extract and Ocimum sanctum extract treated groups compared to control group. The combination of extracts (50 mg/kg each) activity was comparable to standard drug Fluoxetine. Treatment with extracts does not modify the locomotor activity of mice, which indicates that they exert antidepressant effects without modifying significantly locomotor activity. Therefore, the present study confirms the combination of alcoholic extract of Piper nigrum (AEPN) fruit and aqueous extract of Ocimum sanctum (AEOS) possessing additive/synergistic antidepressant activity.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Pravin O. Patil ◽  
Sanjay B. Bari

The present study refers to the synthesis of new antidepressant candidates using the indole scaffold. In an attempt to identify potential lead antidepressant agents, a number of indole molecules, incorporating isoxazoline, were synthesized by microwave-assisted synthesis. The antidepressant activity of the synthesized compounds(3a–3n)was evaluated by forced swim test in mice and their locomotor activity was assessed using actophotometry. The present paper showed significant antidepressant activity for all compounds of the series and no significant change in locomotor activity of mice. Compounds3dand3jwere found to be potent molecules of this series, when compared with the reference drugs imipramine and fluoxetine. It clearly demonstrated that replacement of aromatic core by appropriate heterocycles such as pyridine and pyrrole on the 5-(1H-Indol-3-yl)-3-(Phenyl)-4,5-dihydroisoxazoline(3a)would generate more potent derivatives. Thus, these compounds can serve as potential leads for further antidepressant studies.


Author(s):  
Vasudha Bakshi ◽  
Devender Palsa ◽  
Nazia Begum ◽  
Jeevan Kommidi ◽  
Kapishwar Singh ◽  
...  

Objective: The aim of this study is to investigate the effects of pterostilbene on the behavior of mice and oxidative stress under the influence of Ketamine induced schizophrenia model. Methods: Schizophrenia was induced in mice by ketamine (50mg/kg/day, i.p, for 14 days). The treatment effect of pterostilbene (10 and 20 mg/kg/day, p.o, for 14 days) were verified on Actophotometer, Y-maze, Forced swim test (FST), open field apparatus, acetylcholinesterase activity and anti oxidant stress-related biomarker (Catalase, GSH, TBARS, SOD) levels in brain tissues. Results: Pterostilbene decreased TBARS, AChE and increased SOD, CAT, GSH levels in mice brain when compared with control group. It also improved spatial recognition memory, decreased mobility time, decreased exploratory behaviour and locomotor activity as evident by improved performance in Y-Maze task, Forced swim test, Open field test and Locomotor activity test. Conclusion: Pterostilbene has a neuroprotective role related atleast in part to an antioxidant mechanism and Anti AChE activity, which could be explored as more effective therapies of schizophrenia and other psychiatric diseases.


2017 ◽  
Vol 1 ◽  
pp. 247054701771298 ◽  
Author(s):  
Kaziya M Lee ◽  
Michal A Coelho ◽  
Kimberly R Sern ◽  
MacKayla A Class ◽  
Mark D Bocz ◽  
...  

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.


2014 ◽  
Vol 64 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Janko Samardžić ◽  
Laslo Puškaš ◽  
Miljana Obradović ◽  
Dijana Lazić-Puškaš

Abstract It has been shown in electrophysiological studies that the ligand L-655,708 possesses a binding selectivity and a moderate inverse agonist functional selectivity for α5-containing GABA-A receptors. The present study is aimed to investigate the antidepressant effects of the ligand L-655,708 in the forced swim test (FST) and its impact on locomotor activity in rats. The behavior of the animals was recorded with a digital camera, and the data were analyzed by one-way ANOVA, followed by Dunnett’s test. In FST, L-655,708 significantly decreased immobility time at a dose of 3 mg/kg after a single and repeated administration (p<0.05), exerting acute and chronic antidepressant effects. However, it did not induce significant differences in the time of struggling behavior during FST. Furthermore, L-655,708 did not show a significant effect on locomotor activity (p>0.05). These data suggest that negative modulation at GABA-A receptors containing the α5 subunit may produce antidepressant effects in rats. These effects were not confounded by locomotor influences.


2021 ◽  
Author(s):  
◽  
Stephen George Mathew

<p>Introduction: Drug addiction is a chronic and relapsing disorder that has widespread socioeconomic and health consequences. Globally, there are over 29.5 million people who are drug dependent, and New Zealand has one of the highest rates of drug use rates in the developed world. Currently, there are no Food and Drug Administration (FDA) approved pharmacotherapies that target psychostimulant addiction. Kappa opioid receptor (KOPr) agonists are being studied as a potential pharmacotherapy as it utilizes the brain’s own mechanism for controlling reward, however, KOPr agonists have unwanted side effects such as dysphoria and sedation. This thesis explores the KOPr agonists Salvinorin A (Sal A), a naturally-occurring, highly potent and short-acting non-nitrogenous KOPr agonist and a structural analogue, 16-Ethynyl Salvinorin A (16-Ethy). KOPr agonists, such as Sal A have known preclinical anti-addictive and anti-reward effects, therefore, this thesis focuses on evaluating Sal A and 16-Ethy in preclinical tests of reward and side effects.  Methods: Male Sprague-Dawley rats were used in preclinical tests to evaluate common KOPr-mediated side-effects including anxiety (elevated plus maze), depression (forced swim test) sedation (locomotor activity) and aversion (conditioned place aversion). The anti-cocaine effects were also examined using self-administration, dose-response and drug-behavioural sensitisation tests. 16-Ethy was tested at 2 mg/kg in all experiments.  Results: Acute pre-treatment of 16-Ethy induced sedative effects in non-habituated locomotor activity but when rats were habituated prior to administration, no sedation was observed. In contrast, Sal A (2 mg/kg) had sedative effects in habituated, but not in non-habituated locomotor activity (p = 0.0037). Compared to vehicle-treated rats, 16-Ethy and Sal A did not display pro-depressive effects in the forced swim test, show anxiogenic or aversive properties or modulate behavioural sensitisation to cocaine. Cocaine self-administration and dose-response tests were not successfully completed.  Conclusion: At 2 mg/kg, 16-Ethy was found to display sedative effects in non-habituated locomotor activity but not in a habituated paradigm. Compared to vehicle-treated rats, 16-Ethy did not display pro-depressive effects in the forced swim test, or display anxiogenic or aversive properties and did not show significant cocaine sensitisation. Cocaine self-administration and dose-response tests were not successfully completed and will need to be repeated to ascertain the effects of 16-Ethy on them. However, 16-Ethy has shown glimpses of promise as a potential pharmacotherapy against addiction.</p>


2021 ◽  
Author(s):  
◽  
Stephen George Mathew

<p>Introduction: Drug addiction is a chronic and relapsing disorder that has widespread socioeconomic and health consequences. Globally, there are over 29.5 million people who are drug dependent, and New Zealand has one of the highest rates of drug use rates in the developed world. Currently, there are no Food and Drug Administration (FDA) approved pharmacotherapies that target psychostimulant addiction. Kappa opioid receptor (KOPr) agonists are being studied as a potential pharmacotherapy as it utilizes the brain’s own mechanism for controlling reward, however, KOPr agonists have unwanted side effects such as dysphoria and sedation. This thesis explores the KOPr agonists Salvinorin A (Sal A), a naturally-occurring, highly potent and short-acting non-nitrogenous KOPr agonist and a structural analogue, 16-Ethynyl Salvinorin A (16-Ethy). KOPr agonists, such as Sal A have known preclinical anti-addictive and anti-reward effects, therefore, this thesis focuses on evaluating Sal A and 16-Ethy in preclinical tests of reward and side effects.  Methods: Male Sprague-Dawley rats were used in preclinical tests to evaluate common KOPr-mediated side-effects including anxiety (elevated plus maze), depression (forced swim test) sedation (locomotor activity) and aversion (conditioned place aversion). The anti-cocaine effects were also examined using self-administration, dose-response and drug-behavioural sensitisation tests. 16-Ethy was tested at 2 mg/kg in all experiments.  Results: Acute pre-treatment of 16-Ethy induced sedative effects in non-habituated locomotor activity but when rats were habituated prior to administration, no sedation was observed. In contrast, Sal A (2 mg/kg) had sedative effects in habituated, but not in non-habituated locomotor activity (p = 0.0037). Compared to vehicle-treated rats, 16-Ethy and Sal A did not display pro-depressive effects in the forced swim test, show anxiogenic or aversive properties or modulate behavioural sensitisation to cocaine. Cocaine self-administration and dose-response tests were not successfully completed.  Conclusion: At 2 mg/kg, 16-Ethy was found to display sedative effects in non-habituated locomotor activity but not in a habituated paradigm. Compared to vehicle-treated rats, 16-Ethy did not display pro-depressive effects in the forced swim test, or display anxiogenic or aversive properties and did not show significant cocaine sensitisation. Cocaine self-administration and dose-response tests were not successfully completed and will need to be repeated to ascertain the effects of 16-Ethy on them. However, 16-Ethy has shown glimpses of promise as a potential pharmacotherapy against addiction.</p>


2017 ◽  
Vol 12 (4) ◽  
pp. 410 ◽  
Author(s):  
Ajaykumar Rikhabchand Surana ◽  
Rajendra Dayaram Wagh

<p class="Abstract">Hamelia patens is used in folk medicine in the treatment of nervous shock. The present study deals to evaluate the antidepressant-like effects of chloroform and methanol extracts of H. patens on the performance of male mice and GC-MS profiling of bioactive extract. Mice were given extracts orally in acute doses of 100 and 200 mg/kg daily for 7 days and then subjected to forced swim test, tail suspension test and open field test. Imipramine (10 mg/kg/day, p.o.) and  fluxetamine (10 mg/kg/day, p.o.) were used as the standard in forced swim test and tail suspension test  respectively. GC-MS profiling of chloroform extract was performed to find out the chemical constituents in bioactive fraction. After one-week treatment, the chloroform extract (100 and 200 mg/kg/day, p.o.) significantly reduced immobility time in forced swim test and tail suspension test (p&lt;0.05). All extracts did not show any significant change in the locomotor activity in open field test. These data indicate that the extract of H. patens possesses antidepressant-like properties in mice without any significant effect on locomotor activity.</p><p><strong>Video Clip of Methodology</strong>:</p><p>4 min 06 sec:   <a href="https://www.youtube.com/v/DDJzDqiwCKU">Full Screen</a>   <a href="https://www.youtube.com/watch?v=DDJzDqiwCKU">Alternate</a></p>


2013 ◽  
Vol 141 (9-10) ◽  
pp. 582-585 ◽  
Author(s):  
Janko Samardzic ◽  
Dragana Jadzic ◽  
Milan Radovanovic ◽  
Jasna Jancic ◽  
Dragan Obradovic ◽  
...  

Introduction. The trans-isomer of resveratrol is the active ingredient of Poligonum cuspidatum, known for its medicinal properties and traditionally used in the treatment of neuropsychiatric disorders. It is also found abundantly in the skin of red grapes and red wine. Previous studies have suggested that trans-resveratrol demonstrates a variety of pharmacological activities including antioxidant, anti-inflammatory, as well as neuroprotective properties and procognitive effects. Objective. The goal of the present study was to examine the influence of trans-resveratrol on behavior in rats and its antidepressant properties. Methods. Male Wistar rats were treated intraperitoneally (i.p.) with the increasing doses of trans-resveratrol (5, 10 and 20 mg/kg) or vehicle (dimethyl sulfoxide - DMSO), 30 minutes before testing of the spontaneous locomotor activity or forced swimming. For the experiments, the behavior of the animals was recorded by a digital camera, and the data were analyzed by one-way ANOVA, followed by Tukey post-hoc test. Results. Testing of spontaneous locomotor activity, after the application of vehicle or increasing doses of trans-resveratrol, showed no statistically significant difference between groups (p>0.05). In the forced swim test, one-way ANOVA indicated statistically significant effects of trans-resveratrol (p<0.001). Tukey post-hoc test showed that resveratrol significantly decreased immobility time at the doses of 10 mg/kg and 20 mg/kg, manifesting the acute antidepressant-like effects. There were no statistically significant differences between the resveratrol treatment of 5 mg/kg and vehicle (p>0.05). Conclusion. The results from our study suggest that trans-resveratrol produces significant effects in the central nervous system. After single application, it has acute antidepressant effects, but without influence on locomotor activity.


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