Lactoferrin Suppresses Decreased Locomotor Activities by Improving Dopamine and Serotonin Release in the Amygdala of Ovariectomized Rats

Background: Decreases in female hormones not only affect bone metabolism and decrease bone mass, but also affect the central nervous system, causing brain disorders such as depression and dementia. Administration of estradiol by hormone replacement therapy can improve dementia, while reduced estradiol in ovariectomized (OVX) model rats can reduce both bone density and locomotor activity. The antidepressant fluvoxamine, which is widely used in clinical practice, can improve this effect on locomotor reduction. Similarly, lactoferrin (LF) can reportedly improve inhibitory locomotion due to stress. Objective: In this study, we examined the effect of LF on neurite outgrowth in vitro and in vivo using PC12 cells and rats, respectively. Methods: We performed an in vivo study in which 8-week-old female OVX rats were administered LF five days a week for 6 weeks from the day after surgery. After administration was completed, spontaneous locomotor activity in the dark period, immobility time in a forced swim test, and release amount of dopamine and serotonin in the brain were measured. Results: LF was found to have a neurite outgrowth function in PC12 cells. Moreover, LF was found to improve OVX-induced decreases in locomotor activity and increases in immobility time in the forced swim test. Furthermore, administration of LF elicited significant recovery of decreased dopamine and serotonin release in the brains of OVX group rats. Conclusion: These results strongly suggest that LF improved OVX-induced decreases in momentum during the dark period and, moreover, that release of dopamine and serotonin in the brain was involved in this effect.

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

International Journal of Pharmaceutical Sciences Review and Research ◽

10.47583/ijpsrr.2021.v70i02.020 ◽

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.

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EVALUATION OF ANTISTRESS ACTIVITY OF ETHANOLIC EXTRACT OF CHROMOLAENA ODORATA LEAVES IN ALBINO WISTAR RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i11.35452 ◽

2019 ◽

pp. 50-55

Author(s):

VANITA KANASE ◽

SANA SHAIKH

Keyword(s):

Locomotor Activity ◽

Wistar Rats ◽

Forced Swim Test ◽

Ethanolic Extract ◽

Force Swim Test ◽

Chromolaena Odorata ◽

Biochemical Alterations ◽

Swim Test ◽

Induced Stress ◽

Immobility Time

Objective: The objective of this study was to study the effect of ethanolic extract of Chromolaena odorata (EECO) Linn. on acute restraint stress (ARS)-induced stress-like behavior and biochemical alterations in albino Wistar rats. Methods: The ARS was induced by immobilizing the rats for a period of 12 h using rodent restraint device preventing them from any physical movement. Immediately, after 12 h rats were released and doses were given to each rat. 40 min post-release various behavioral parameters such as immobility time in force swim test and tail suspension test (TST), locomotor activity in open field test (OFT), and oxidative stress parameters and biochemical alterations in rat brain tissue were also performed. Statistical Analysis: Expression of data was done as mean±standard error of mean. The normally distributed data were subjected to one-way ANOVA followed by Dunnett’s test. p<0.05 was considered statistically significant. Results: Experimental findings revealed that rats subjected to ARS exhibited significant increase in immobility time in forced swim test and TST models, decrease in locomotor activity in OFT model, and increase in malondialdehyde formation and impaired superoxide dismutase, and catalase activities in hippocampus and cerebral cortex as compared to non-stressed rats. EECO treatment (250 mg/kg and 500 mg/kg) significantly attenuated immobility time, locomotion, and restored the antioxidant enzymes after ARS. Conclusion: EECO significantly alleviated ARS-induced stress-like behavior.

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Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

Molecules ◽

10.3390/molecules24234218 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4218 ◽

Cited By ~ 3

Author(s):

Koprdova ◽

Csatlosova ◽

Durisova ◽

Bogi ◽

Majekova ◽

...

Keyword(s):

Forced Swim Test ◽

Behavioral Assessment ◽

Dopamine Neurons ◽

Neuroleptic Drug ◽

Swim Test ◽

Forced Swim ◽

Reuptake Inhibition ◽

Immobility Time ◽

Dopamine Reuptake

SMe1EC2M3 is a pyridoindole derivative related to the neuroleptic drug carbidine. Based on the structural similarities of SMe1EC2M3 and known serotonin (5-HT), norepinephrine, and dopamine reuptake inhibitors, we hypothesized that this compound may also have triple reuptake inhibition efficacy and an antidepressant-like effect. PreADMET and Dragon software was used for in silico prediction of pharmacokinetics and pharmacodynamics of SMe1EC2M3. Forced swim test was used to evaluate its antidepressant-like effects. Extracellular in vivo electrophysiology was used to assess 5-HT, norepinephrine, and dopamine reuptake inhibition efficacy of SMe1EC2M3. PreADMET predicted reasonable intestinal absorption, plasma protein binding, and blood-brain permeability for SMe1EC2M3. Dragon forecasted its efficiency as an antidepressant. Using behavioral measurements, it was found that SMe1EC2M3 decreased immobility time and increase swimming time during the forced swim test (FST). Electrophysiological investigations showed that SMe1EC2M3 dose-dependently suppressed the excitability of 5-HT neurons of the dorsal raphe nucleus (DRN), norepinephrine neurons of the locus coeruleus (LC), and dopamine neurons of the ventral tegmental area (VTA). The SMe1EC2M3-induced suppression of 5-HT, norepinephrine, and dopamine neurons was reversed by the antagonists of serotonin-1A (5-HT1A; WAY100135), α-2 adrenergic (α2, yohimbine), and dopamine-2 receptors (D2, haloperidol), respectively. We conclude that SMe1EC2M3 is prospective triple 5-HT, norepinephrine, and dopamine reuptake inhibitor with antidepressant-like properties, however future studies should be performed to complete the pharmacological profiling of this compound.

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Antidepressant effects of an inverse agonist selective for α5 GABA-A receptors in the rat forced swim test

Acta veterinaria ◽

10.2478/acve-2014-0006 ◽

2014 ◽

Vol 64 (1) ◽

pp. 52-60 ◽

Cited By ~ 3

Author(s):

Janko Samardžić ◽

Laslo Puškaš ◽

Miljana Obradović ◽

Dijana Lazić-Puškaš

Keyword(s):

Locomotor Activity ◽

Forced Swim Test ◽

Digital Camera ◽

Repeated Administration ◽

Inverse Agonist ◽

Gaba A ◽

Swim Test ◽

Forced Swim ◽

Antidepressant Effects ◽

Immobility Time

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.

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Low molecular mass chondroitin sulfate suppresses chronic unpredictable mild stress-induced depression-like behavior in mice

Acta Pharmaceutica ◽

10.2478/acph-2018-0028 ◽

2018 ◽

Vol 68 (3) ◽

pp. 361-371 ◽

Cited By ~ 1

Author(s):

Xiao-Ming Si ◽

Yu-Hua Tian ◽

Sha-Sha Zhang ◽

Hua Gao ◽

Kun Liu ◽

...

Keyword(s):

Locomotor Activity ◽

Chondroitin Sulfate ◽

Molecular Mass ◽

Forced Swim Test ◽

Mechanisms Of Action ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sucrose Consumption ◽

Swim Test ◽

Immobility Time

Abstract The present study is aimed at testing the antidepressant--like effects and probable mechanisms of action of low molecular mass chondroitin sulfate (LMMCS) on depression induced by chronic unpredictable mild stress (CUMS) in mice. Four weeks of CUMS exposure resulted in depressive-like behavior, expressed by a significant decrease in the locomotor activity and sucrose consumption and increased immobility time in the forced swim test. Further, there was a significant reduction of 5-HT level in the hippocampus region of depressed mice. Treatment of mice for four weeks with LMMCS ameliorated significantly both the behavioral and biochemical changes induced by CUMS. These novel results suggest that LMMCS produces an antidepressant-like effect in mice subjected to CUMS, which might be related, at least in part, to the increase of 5-HT concentration in the hippocampus.

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The effects of resveratrol on rat behaviour in the forced swim test

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1310582s ◽

2013 ◽

Vol 141 (9-10) ◽

pp. 582-585 ◽

Cited By ~ 2

Author(s):

Janko Samardzic ◽

Dragana Jadzic ◽

Milan Radovanovic ◽

Jasna Jancic ◽

Dragan Obradovic ◽

...

Keyword(s):

Locomotor Activity ◽

Forced Swim Test ◽

Digital Camera ◽

Spontaneous Locomotor Activity ◽

Swim Test ◽

Forced Swim ◽

Immobility Time ◽

Significant Difference ◽

Post Hoc ◽

One Way Anova

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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Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

Current Bioactive Compounds ◽

10.2174/1573407216666200203142722 ◽

2020 ◽

Vol 16 (9) ◽

pp. 1319-1327

Author(s):

Ferdous Khan ◽

Syed A. Kuddus ◽

Md. H. Shohag ◽

Hasan M. Reza ◽

Murad Hossain

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Reduced Glutathione ◽

Forced Swim Test ◽

Tail Suspension Test ◽

Glutathione Depletion ◽

Swim Test ◽

Stress Markers ◽

Immobility Time ◽

Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

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

Journal of Psychopharmacology ◽

10.1177/0269881121996883 ◽

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.

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The role of CYP2D in rat brain in methamphetamine-induced striatal dopamine and serotonin release and behavioral sensitization

Psychopharmacology ◽

10.1007/s00213-021-05808-9 ◽

2021 ◽

Author(s):

Marlaina R. Stocco ◽

Ahmed A. El-Sherbeni ◽

Bin Zhao ◽

Maria Novalen ◽

Rachel F. Tyndale

Keyword(s):

Neurotransmitter Release ◽

Behavioral Sensitization ◽

Serotonin Release ◽

Striatal Dopamine ◽

Irreversible Inhibitor ◽

Drug Concentrations ◽

Metabolite Concentrations ◽

The Brain

Abstract Rationale Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats. Methods To investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release. Results CYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor pretreatment exacerbated stereotypy sensitization and enhanced dopamine and serotonin release in the dorsal striatum. Day 1 brain methamphetamine and amphetamine concentrations correlated with dopamine and serotonin release, which in turn correlated with the stereotypy response slope across sessions (i.e., day 1 through day 7), used as a measure of sensitization. Conclusions CYP2D-mediated methamphetamine metabolism in the brain is sufficient to alter behavioral sensitization, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

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Failure to detect the action of antidepressants in the forced swim test in Swiss mice

Acta Neuropsychiatrica ◽

10.1017/neu.2017.33 ◽

2017 ◽

Vol 30 (3) ◽

pp. 158-167 ◽

Cited By ~ 3

Author(s):

Patrick R. Suman ◽

Nathalia Zerbinatti ◽

Lais Cristina Theindl ◽

Karolina Domingues ◽

Cilene Lino de Oliveira

Keyword(s):

Sodium Butyrate ◽

Antidepressant Treatment ◽

Forced Swim Test ◽

Dark Cycle ◽

Swim Test ◽

Swiss Mice ◽

Forced Swim ◽

Immobility Time ◽

Effective Doses ◽

High Doses

ObjectiveThe aims of this study were to replicate previously published experiments and to modify the protocol to detect the effects of chronic antidepressant treatment in mice.MethodsMale Swiss mice (n=6–8/group) housed in reversed light/dark cycle were randomly assigned into receive vehicle (10% sucrose), sub-effective doses (1 and 3 mg/kg) or effective doses (10 and 30 mg/kg) of bupropion, desipramine, and fluoxetine and a candidate antidepressant, sodium butyrate (1–30 mg/kg) per gavage (p.o.) 1 h before the forced swim test (FST). Treatments continued daily for 7 and 14 days during retests 1 and 2, respectively. In an additional experiment, mice received fluoxetine (20 mg/kg) or vehicle (10% sucrose or 0.9% saline) p.o. or i.p. before the FST. Mice housed in reversed or standard light/dark cycles received fluoxetine (20 mg/kg) prior FST. Video recordings of behavioural testing were used for blind assessment of the outcomes.ResultsAccording to the expected, doses of antidepressants considered sub-effective failed to affect the immobility time of mice in the FST. Surprisingly, acute and chronic treatment with the high doses of bupropion, desipramine, and fluoxetine or sodium butyrate also failed to reduce the immobility time of mice in the FST. Fluoxetine 20 mg/kg was also ineffective in the FST when injected i.p. or in mice housed in normal light/dark cycle.ConclusionData suggest the lack of efficacy of orally administered bupropion, desipramine, fluoxetine in the FST in Swiss mice. High variability, due to high and low immobility mice, may explain the limited effects of the treatments.

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