Profile of a short-acting κ-antagonist, LY2795050, on self-grooming behaviors, forced swim test and locomotor activity: sex comparison in mice

2021 ◽  
pp. 026988112199688
Author(s):  
Eduardo R Butelman ◽  
Caroline Baynard ◽  
Bryan D McElroy ◽  
Thomas E Prisinzano ◽  
Mary Jeanne Kreek
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Male And Female ◽  
Short Acting ◽  
Swim Test ◽  
Central Nervous System Dysfunction ◽  
Forced Swim ◽  
Males And Females ◽  
The Impact ◽  
Κ Receptor

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.

scholarly journals Evaluation of Additive or Synergistic Effect of Piper nigram and Ocimum sanctum Extracts for their Antidepressant Activity

2021 ◽  
Vol 70 (2) ◽  
Author(s):  
K. Mohana Rao ◽  
Siva B. ◽  
Mahendra U. ◽  
Vinay K. ◽  
A. Narendra Babu ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Piper Nigrum ◽  
Ocimum Sanctum ◽  
Alcoholic Extract ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time ◽  
Wide Range

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.

scholarly journals Synthesis and Antidepressant Activity of Some New 5-(1H-Indol-3-yl)-3-(substituted aryl)-4,5-dihydroisoxazoline Derivatives

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Pravin O. Patil ◽  
Sanjay B. Bari
Keyword(s):  
Locomotor Activity ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Microwave Assisted Synthesis ◽  
Antidepressant Agents ◽  
Microwave Assisted ◽  
Swim Test ◽  
Forced Swim ◽  
Significant Change

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.

scholarly journals Neuroprotective effect of pterostilbene on ketamine induced schizophrenia in mice

2016 ◽  
Vol 1 (03) ◽  
pp. 96-103 ◽  
Author(s):  
Vasudha Bakshi ◽  
Devender Palsa ◽  
Nazia Begum ◽  
Jeevan Kommidi ◽  
Kapishwar Singh ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Open Field ◽  
Forced Swim Test ◽  
Neuroprotective Effect ◽  
Oxidant Stress ◽  
Acetylcholinesterase Activity ◽  
Control Group ◽  
Swim Test ◽  
Forced Swim ◽  
Y Maze

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.

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 Does the antidepressant-like effect of mirtazapine and venlafaxine differ between male and female rats?

Salud Mental ◽  
2020 ◽  
Vol 43 (1) ◽  
pp. 3-9
Author(s):  
Adriana Álvarez Silva ◽  
Alonso Fernández-Guasti
Keyword(s):  
Forced Swim Test ◽  
Treatment Options ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Swim Test ◽  
Male And Female Rats ◽  
Males And Females ◽  
New Treatment ◽  
Global Health Problem

Introduction. Depression is a global health problem with nearly 350 million people affected, mainly women. However, nowadays a rising amount of men are being diagnosed. This makes necessary the screening of new treatment options that are effective in women as well as in men. Objective. To analyze if the administration of mirtazapine and venlafaxine to male and female rats shows a sex-related antidepressant-like effect, and the possible associated neurochemical mechanisms. Method. Mirtazapine (40 mg/kg) or venlafaxine (60 mg/kg) were administered subchronically to young adult male and female (ovariectomized and steroid-primed) rats, and their antidepressant-like effects were evaluated using the forced swim test (FST). The active behaviors, swimming and climbing, were also analyzed. Results. a) mirtazapine and venlafaxine reduced immobility in the FST in males and females; b) both antidepressants increased climbing and swimming in male rats; c) in female rats, mirtazapine and venlafaxine only increased swimming. Discussion and conclusion. In males, the effects of mirtazapine and venlafaxine seem to be produced by the activation of the serotonergic and noradrenergic systems. Conversely, estradiol might be modulating the mechanisms of action of both antidepressants in females producing only an increased swimming and suggesting the participation of the serotonergic system.

Stressors affect the response of male and female rats to clomipramine in a model of behavioral despair (forced swim test)

2005 ◽  
Vol 520 (1-3) ◽  
pp. 100-107 ◽  
Author(s):  
Daniele Consoli ◽  
Julia Fedotova ◽  
Vincenzo Micale ◽  
Nikolay S. Sapronov ◽  
Filippo Drago
Keyword(s):  
Forced Swim Test ◽  
Female Rats ◽  
Male And Female ◽  
Behavioral Despair ◽  
Swim Test ◽  
Forced Swim ◽  
Male And Female Rats
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