Duration Of Immobility In Forced Swim Test Research Articles

Repeated finasteride administration promotes synaptic plasticity and produces antidepressant- and anxiolytic-like effects in female rats.

Finasteride is used in female-pattern hair loss, hirsutism, and polycystic ovarian syndrome. It inhibits 5α-reductase, which is an important enzyme in the biosynthesis of neurosteroids. The effects of finasteride treatment on mental health in female patients as well as the effects of repeated/chronic finasteride administration in female rodents are still unknown. Accordingly, in our study, we administered finasteride (10, 30, or 100 mg/Kg, s.c.) for 6 days in female rats and evaluated behavior, plasma steroid levels, and synaptic plasticity. Depression-like behavior was evaluated using forced swim test (FST) and splash test. Anxiety-like behavior was evaluated using novelty-suppressed feeding task (NSFT), elevated plus maze (EPM), open field test (OFT), and light-dark test (LDT). Plasma steroid levels were assessed using ELISA and synaptic plasticity by field potential recordings. We observed that finasteride decreased total immobility duration in FST, indicating antidepressant-like effect and decreased the latency to first bite in NSFT, showing anxiolytic-like effect. We also found a significant increase in plasma estradiol and a significant decrease in plasma corticosterone level. Furthermore, field potential recordings showed that finasteride increased hippocampal long-term potentiation. These results indicate that repeated finasteride administration in female rats may have antidepressant- and anxiolytic-like effect, which might be mediated by enhanced estradiol levels or decreased corticosterone levels. Further studies are required to validate the molecular mechanisms underlying the effects of finasteride in female rats. Understanding the mechanisms will help us in developing novel neurosteroid-based therapeutics in the treatment of neuropsychiatric disorders in women.

Anti-oxidant and neuro-modulatory effects of bioactive Byttneria pilosa leaf extract in swiss albino mice using behavioral models.

Byttneria pilosa, a flowering plant from the Malvaceae family traditionally used to treat ailments such as boils and scabies, is here investigated for its potential health benefits. The study focused on evaluating its antioxidant and antidiabetic properties in vitro, as well as the in vivo anxiolytic and antidepressant activities of the methanol extract of B. pilosa leaf (MEBP). The study employed various assays to evaluate antioxidant activity, including 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power capacity, and quantification of the total phenolic and flavonoid contents of MEBP. Additionally, anxiolytic and antidepressant activities were evaluated through four tests: elevated plus-maze test (EPMT), light-dark box test (LDBT), forced swimming test (FST), and tail suspension test (TST). Antidiabetic effect was determined using α-amylase inhibition assay. Docking analysis was performed using BIOVIA and Schrödinger Maestro (v11.1), and the absorption, distribution, metabolism, and excretion/toxicity (ADME/T) properties of bioactive substances were investigated using a web-based technique. MEBP exhibited moderate antioxidant activity in DPPH radical scavenging and reducing power capacity assays, with a dose-dependent response. The total phenolic and flavonoid contents measured were 70 ± 1.53mg and 22.33 ± 1.20mg, respectively. MEBP demonstrated significant effects in α-amylase inhibition comparable to acarbose. In behavioral tests, MEBP dose-dependently altered time spent in open arms/light box and closed arms/dark box, indicating anxiolytic effects. Moreover, MEBP significantly reduced immobility duration in FST and TST, suggesting antidepressant properties. Molecular docking analysis revealed favorable interactions between beta-sitosterol and specific targets, suggesting the potential mediation of anxiolytic and antidiabetic effects. Overall, MEBP exhibits notable anxiolytic and antidepressant properties, along with moderate antioxidant and antidiabetic activities.

CRISPR/Cas9 based gene editing of Frizzled class receptor 6 (FZD6) reveals its role in depressive symptoms through disrupting Wnt/β-catenin signaling pathway

IntroductionAs one of the common psychiatric diseases, depression poses serious threats to human health. Although many genes have been nominated for depression, few of them were investigated in details at the molecular level. ObjectivesTo demonstrate Frizzled class receptor 6 (FZD6) functions in depression through disrupting Wnt/β-catenin signal pathway. MethodsThe FZD6 edited cell line and mouse model were generated by using CRISPR/Cas9 technique. The expression of key genes and proteins in Wnt/β-catenin pathway was determined by qRT-PCR and Western blotting, respectively. Animal behavioral tests, including open field test (OFT), elevated plus maze test (EPM), forced swimming test (FST), tail suspension test (TST), and sucrose preference test (SPT), were employed to determine anxiety- and depressive-like behaviors. Immunofluorescent staining was used to assess cell proliferation in the hippocampus of mouse brain. ResultsAmong patients with depression, FZD6, one of the receptors of Wnt ligand, was significantly decreased. In CRISPR/Cas9-based FZD6 knockdown cells, we showed that FZD6 plays a significant role in regulating expression of genes involved in Wnt/β-catenin pathway. Subsequently behavioral studies on Fzd6 knockdown mice (with a 5-nucleotide deletion; Fzd6-Δ5) revealed significant changes in depressive symptoms, including increased immobility duration in FST, less preference of sucrose in SPT, reduction of distance traveled in OFT, and decreased time spent in open arms in EPM. Immunofluorescent staining showed decreased cell proliferation in the hippocampus of Fzd6-Δ5 mice with reduced number of Ki67+ and PCNA+ cells.Moreover, decreased Gsk3β mRNA expression, phosphorylated GSK3β, and cytoplasmic β-catenin in the hippocampus of Fzd6-Δ5 mice provided further evidence supporting the role of Fzd6 in depression. ConclusionTogether, above findings proved the significant role of FZD6 in depression through its effect on hippocampal cell proliferation and its ability to regulate canonical Wnt/β-catenin pathway.

Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919. Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot. Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24h after an intraperitoneal (i.p.) injection of ketamine (10mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24h after the intragastric (i.g.) administration of YL-0919 (2.5mg/kg), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622. Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.

Swimming exercise ameliorates depressive-like behavior by anti-inflammation activity, rebalancing gut Escherichia coli and Lactobacilli

Major depressive disorder (MDD) is a common mental disease with high morbidity, recurrence and mortality and is a serious global health problem.Aerobic exercise produces beneficial effects on depression and associated comorbidities.Swimming exercise with high motor complexity may be particularly beneficial for patients with depression.We hypothesized that swimming exercise improves various types of depression-like behaviors and these effects are related to improved immune and inflammatory response by regulating microbiota-gut-brain axis.We established the Lipopolysaccharides (LPS)/Chronic unpredictable stress (CUS) mice model of depression. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant-like activity.Swimming exercise significantly decreased the duration of immobility in FST and TST.We found that swimming exercise could significantly decrease the levels of pro-inflammatory cytokines in the central nervous system (CNS). Shifts in the composition of the gut microbiota were significant in depression model induced by LPS/CUS, notably as decreases in lactobacilli and increases in escherichia coli (E. coli), which were reversed byswimming exercise. Current study indicated that swimming exercise has huge potential for antidepressant therapy, and gut microbiotaplays an important role inregulating inflammation. We are pleased that current can study reveal a potentially promising method with less adverse reaction for combating depression and open up an important new area for future research.

Antidepressant and Anxiolytic Effects and Subacute Toxicity of the Aerial Parts of Psychotria ankasensis J.B.Hall (Rubiaceae) in Murine Models.

Background The present study aimed at validating the traditional use and toxicity profile of a methanolic extract of the aerial parts of Psychotria ankasensis in alleviating depression and anxiety disorders. Method The antidepressant effect of methanolic extract of Psychotria ankasensis (PAE 30, 100, and 300 mg/kg, p.o.) was assessed in mice using the forced swim test (FST) and the tail suspension test (TST). The plant's anxiolytic potential was also evaluated in mice using the elevated plus-maze (EPM) and the open field tests (OFT). The subacute toxicity was assessed via oral administration of PAE at doses of 100, 300, and 1000 mg/kg in rats for 28 days. Results PAE 100 and 300 mg/kg showed antidepressant-like properties by significantly (at least p < 0.05) decreasing the frequency and duration of immobility in FST and TST. PAE (100 and 300 mg/kg) also showed a significant (at least p < 0.05) anxiolytic effect in both EPM and OFT. In the EPM test, Emax for PAE and diazepam were 92.52 ± 40.11% and 85.95 ± 45.92%, respectively, whereas Emax was approximately 100% for both test drugs in the OFT. Subacute administration of PAE did not reveal any toxic effects with respect to organ weight index, haematological, serum biochemical, and histopathological parameters. Conclusions Methanolic extract of P. ankasensis exhibited antidepressant-like and anxiolytic-like effects devoid of significant toxicity at the doses tested in murine models.

Schisandra chinensis ameliorates depressive-like behaviors by regulating microbiota-gut-brain axis via its anti-inflammation activity.

The present study aimed to examine the antidepressant actions of the composition fractions of Schisandra chinensis using LPS-induced mice. Animals were treated with total extracts (SCE), lignans (SCL), polysaccharides (SCPS), and essential oil (SCVO), and then subjected to behavioral tests. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant activity. Total extracts and lignans significantly decreased the duration of immobility in FST and TST. We found that treatment with SCE and SCL could significantly decrease the levels of pro-inflammatory cytokines both in the periphery and central nervous system (CNS). This was confirmed by the histopathological examination of the colon. The RT-PCR results demonstrated that SCE and SCL could greatly inhibit the TLR4/NF-κB/IKKα signaling pathway. In addition, the concentrations of Butyric acid and Propionic acid were upregulated by the administration, and the decreased diversity of intestinal microbiota and alterations of the relative proportions of Bacteroidetes and Firmicutes phylum members, Barnesiella and Lactobacillus genus members in LPS-induced mice were restored as well. All results suggested that lignans is the effective fraction of S.chinensis to ameliorating depressive disorders, which its anti-inflammation activity possibly involved in the bidirectional connection between gut microbiota and brain.

Synthesis of 1,3,4-oxadiazoles derivatives with antidepressant activity and their binding to the 5-HT1A receptor.

In this study, two series of 1,3,4-oxadiazole derivatives were designed and synthesized using the forced swimming test (FST) model to test the antidepressant activity of the target compound in vivo. Five compounds with potential activity were selected from the FST model to test affinity with 5-HT1A receptor in vitro. The results of the FST experiment showed that compound N-(3-((5-((4-chlorobenzyl)thio)-1,3,4-oxadiazol-2-yl)methoxy)phenyl)acetamide (10g) showed the best antidepressant activity (DID = 58.93, percentage decrease in immobility duration in FST), similar to the activity of positive drug fluoxetine. Compound 10g also exhibited the most potent binding affinity to 5-HT1A receptors (Ki = 1.52 nM). The results of the in vivo 5-HT concentration estimation in mice showed that compound 10g may have an effect on the brain. The experimental results of exploratory activity in mice showed that compound 10g did not affect spontaneous activity in the open-field test model. Molecular docking was used to study the binding mode of compound 10g and the 5-HT1A receptor. Compound 10g showed significant interactions with residues at the active site on the 5-HT1A receptor. The physicochemical and pharmacokinetic properties of the target compounds were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.

Effect of Electroacupuncture at GV20 on Sleep Deprivation-Induced Depression-Like Behavior in Mice.

Accumulating evidence suggests that sleep deprivation (S-Dep) is a critical risk factor for depression. Electroacupuncture (EA) treatment has been reported to ameliorate posttraumatic stress disorder- (PSTD-) like behavior and enhance hippocampal neurogenesis. However, whether EA treatment has any beneficial effect on S-Dep-induced depression-like behavior is still unknown. In the present study, we focused on whether EA at Baihui (GV20) can ameliorate the deterioration effect of S-Dep in mice. Mice were randomly divided into normal, S-Dep, S-Dep + EA, and S-Dep + sham EA groups. Cognitive behavior test and in vitro assay were performed separately to avoid the influence of behavior test on synaptic transmission and protein expression. Depression-like behaviors were determined by forced swimming test (FST), tail suspension test (TST), and Morris water maze (MWM). Neurogenesis was identified by BrdU, DCX, and NeuN immunofluorescence staining. In vitro long-term potentiation was detected by high frequency stimulation (HFS) at Schaffer collateral-CA1 synapses in hippocampal slices. Brain-derived neurotropic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein expression level were assayed by western blot. Our results indicated that D-Sep mice demonstrated depression-like behaviors determined by prolonged immobility duration in FST and TST; D-Sep mice also manifested spatial memory retention deficit in MWM. Furthermore, EA treatment ameliorated D-Sep-induced depression-like behaviors and spatial memory retention deficit. Mechanically, EA treatment alleviated neuron progenitor cell proliferation and differentiation, ameliorated the field excitatory postsynaptic potentials (fEPSPs) slope impaired by S-Dep, and elevated BDNF/TrkB protein expression. Taken together, our data suggested that EA treatment has a protective effect on S-Dep-induced depression-like behavior and cognitive impairment, which may be through regulating BDNF/TrkB protein expression.

The Antidepressant Effect of Chlorella vulgaris on Female Wistar Rats (Rattus norvegicus Berkenhout, 1769) with Chronic Unpredictable Mild Stress Treatment

Depression is a disabling mental disorder, predicted to become the world's number 2 disability by 2020 by the World Health Organization (WHO, 2018). Chronic stress is one of the triggers for depression, causing an imbalance in brain chemicals and antioxidants levels. Although antidepressant is a common treatment, discomforting side effects has compromised its efficacy, prompting the search for alternative medicines. Chlorella vulgaris is a microalgae famous for its excellent protein and antioxidant content. In this study, C. vulgaris (360 mg/kg p.o.) potency of antidepressant in chronic unpredictable mild stress (CUMS) model of depression in female rats was evaluated compared to amitriptyline (2,25 mg/kg p.o.) for 14 days. Two types of C. vulgaris namely cultivation sourced and commercially-sold, were used. Sucrose preference test, forced swim test (FST) and open field test (OFT) were used as depression-like behaviour test to validate C. vulgaris effect. Adrenal glands were observed to further understand its effect on the stress organ. The CUMS method produced rats with depressive-like behaviour evidently by reduced body weight, sucrose preference, exploring behaviour in OFT, and increased immobility duration in FST. Furthermore, an increase in adrenal weight, fasciculata zone, and reticularis zone was observed. Both C. vulgaris significantly (p&lt;0,05) reversed depressive-like behaviour in rats subjected to CUMS, but not the size of adrenal glands. This finding indicated both types of C. vulgaris has the potential to be an alternative antidepressant but because of the short duration of treatment, it’s speculated that C. vulgaris may not have exhibited enough difference structurally yet.

Studying the behavioral changes in schizophrenic rats induced by chronic exposure to ketamine

Schizophrenia is a chronic and highly complex psychiatric disorder characterised by cognitive dysfunctions, negative and positive symptoms. The major challenge in schizophrenia research is lack of suitable animal models that mimic the core behavioural aspects and symptoms of this devastating psychiatric disorder. In this study, we used classical and atypical antipsychotic drugs to examine the predictive validity of ketamine-enhanced immobility in forced swim test (FST) as a possible animal model for the negative symptoms of schizophrenia. Repeated administration of a subanaesthetic dose of ketamine (0.1 mg / kg b.wt.) for 60 days enhanced the duration of immobility in FST 24 h after the final injection. Suggesting that the effects of ketamine on the duration of immobility in this study was neither due to motor dysfunction nor peripheral neuromuscular blockade. Our results suggest that repeated treatment with subanaesthetic doses of ketamine enhance the duration of immobility in FST, which might be a useful animal model for the negative symptoms (particularly the depressive features) of schizophrenia.

Antidepressant Effects of Oleuropein in Male Mice by Forced Swim Test and Tail Suspension Test

Abstract Objectives: With increasing prevalence of depression in communities and public concern regarding the side effects of synthetic drugs, special attention has recently been paid to identifying natural compounds with antidepressant effects. Oleuropein is an antioxidant polyphenol that is present in the leaves and fruits of different variants of olive. The aim of the present study was to investigate the antidepressant effects of oleuropein in mice by forced swim test (FST) and tail suspension test (TST). Methods: In this experimental study, 50 mice were randomly divided into 5 groups of 10. Group 1 received normal saline; group 2 intraperitoneally received reserpine at 5 mg/kg 18 hours before behavioral testing; group 3, in addition to reserpine, intraperitoneally received oleuropein at 10 mg/kg 15 minutes before behavioral testing; group 4, in addition to reserpine, received fluoxetine at 20 mg/kg; and group 5 received oleuropein at 10 mg/kg for 3 days and then reserpine 18 hours before behavioral testing. Behavioral tests were FST and TST. Finally, the antioxidant capacity and malondialdehyde (MDA) and nitric oxide (NO) levels in the serum and brain of the mice were measured. Results: Reserpine significantly increased the duration of immobility in FST and TST and significantly decreased serum and brain antioxidant capacity, significantly increased MDA levels in the brain and serum, and significantly increased serum NO level (P < 0.05). Oleuropein treatment for 3 days caused a significant decrease of immobility in FST, a significant increase in brain and serum antioxidant capacity, and a significant decrease of brain and serum MDA and NO levels (P < 0.05). Conclusion: Oleuropein was found to exhibit significant antidepressant effects in mice, probably due to its antioxidant activity.

Neurosteroid dehydroepiandrosterone improves active avoidance retrieval and induces antidepressant-like behavior in rats.

Various studies reported beneficial effects of dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), the neurosteroids involved in various brain functions, on synaptic plasticity, neuronal survival, memory, learning and behavior. This study aimed to investigate the behavioral profile of acute DHEA treatment by using active avoidance (AA) task, primarily predictive of the effects on the retrieval-based learning, and by applying forced swim test (FST), for assessment of antidepressant-like potential. Adult male Wistar rats received intraperitoneal injections of either DHEA (2, 10, 20mg/kg) or solvent, 30min prior to testing. DHEA, in a manner resembling an inverted U shape, influenced the retrieval imposed to rats in AA paradigm. The significant improvement of the performance in the retention session was observed following 10mg/kg DHEA treatment and it was not due to the changes in the motor activity, as indicated by unaltered locomotor parameters (inter-trial crossing). Moreover, 10mg/kg of DHEA significantly decreased the duration of immobility in FST, demonstrating antidepressant-like effects. The capability of bicuculline (2mg/kg) to antagonize the effects of DHEA has been evaluated simultaneously. The retrieval-facilitating as well as antidepressant-like effects of 10mg/kg DHEA were counteracted by bicuculline, a competitive antagonist of GABAA receptors, suggesting involvement of GABAergic system. These results support administration of DHEA as potential therapeutic strategy for treating depression and related cognitive impairments, but emphasized the importance of adequate dosing, as DHEA levels that are too high or too low may not be beneficial.

Standardisation and Validation of Acute and Chronic Administration Ketamine at Different Doses to Produce Psychosis Like Behavioural Changes in Mice

Psychosis is a complex mental illness, characterised by positive, negative and cognitive symptoms. NMDA receptor antagonists have been established to induce behavioural as well as biochemical changes in rodents similar to psychotic patients. The aim of the present study was to investigate the effective dose and treatment period of ketamine to induce some behavioural changes. The results suggest that acute treatment of ketamine (50 and 100 mg/kg, i.p.) induced hyperlocomotor activity and reduced step down latency time in passive avoidance test, whereas in effective in forced swim test. Further, with the chronic administration of ketamine (50 and 100 mg/kg, i.p.) effective to produced hyperlocomotor activity, reduced the step down latency time in passive avoidance test and enhanced the immobility duration in forced swim test. Moreover, these behavioural changes persisted for 7 days after the treatment period. Thus, our findings suggest that the chronic administration of Ketamine (50 and 100 mg/kg, i.p.) potential to produce behavioural changes, would serve as an effective tool to screen antipsychotic drugs.

Paeonol attenuates lipopolysaccharide-induced depressive-like behavior in mice

The present study was designed to detect the anti-depressant effects of paeonol and the possible mechanisms in the lipopolysaccharide-induced depressive-like behavior. Open-field test(OFT), tail suspension test(TST) and forced swimming test(FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in mice hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Our results showed that LPS significantly decreased the levels of 5-HT and NE in the hippocampus. LPS also reduced open-field activity, as well as increased immobility duration in FST and TST. Paeonol administration could effectively reverse the alterations in the concentrations of 5-HT, NE and reduce the IL-6 and TNF-α levels. Moreover, paeonol effectively downregulated brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and Nuclear factor-κB (NF-κB) in hippocampal. In conclusion, paeonol administration exhibited significant antidepressant-like effects in mice with LPS-induced depression.

Antidepressant-Like Effect of Lipid Extract of Channa striatus in Chronic Unpredictable Mild Stress Model of Depression in Rats.

This study evaluated the antidepressant-like effect of lipid extract of C. striatus in chronic unpredictable mild stress (CUMS) model of depression in male rats and its mechanism of action. The animals were subjected to CUMS for six weeks by using variety of stressors. At the end of CUMS protocol, animals were subjected to forced swimming test (FST) and open field test followed by biochemical assay. The CUMS protocol produced depressive-like behavior in rats by decreasing the body weight, decreasing the sucrose preference, and increasing the duration of immobility in FST. The CUMS protocol increased plasma corticosterone and decreased hippocampal and prefrontal cortex levels of monoamines (serotonin, noradrenaline, and dopamine) and brain-derived neurotrophic factor. Further, the CUMS protocol increased interleukin-6 (in hippocampus and prefrontal cortex) and nuclear factor-kappa B (in prefrontal cortex but not in hippocampus). The lipid extract of C. striatus (125, 250, and 500 mg/kg) significantly (p < 0.05) reversed all the above parameters in rats subjected to CUMS, thus exhibiting antidepressant-like effect. The mechanism was found to be mediated through decrease in plasma corticosterone, increase in serotonin levels in prefrontal cortex, increase in dopamine and noradrenaline levels in hippocampus and prefrontal cortex, increase in BDNF in hippocampus and prefrontal cortex, and decrease in IL-6 and NF-κB in prefrontal cortex.

Screening of antidepressant activity and estimation of quercetin from Coccinia indica using TLC densitometry

Context: Coccinia indica Naud (Cucurbitaceae) has been traditionally used for the treatment of depression but these claims have not been validated.Objectives: The objective of this study is to investigate antidepressant activity of various extracts and fractions of C. indica aerial parts, and to estimate content of quercetin in the plant using TLC densitometry.Materials and methods: Coccinia indica aerial parts were successively extracted using solvents in increasing order of polarity, namely n-hexane, chloroform, methanol, and water. Various extracts were evaluated for antidepressant activity at doses of 200 or 400 mg/kg, p.o., upon acute administration in mice using the forced swim test (FST). The bioactive extract was partitioned successively using solvents in increasing order of polarity, namely n-hexane, ethyl acetate, and n-butanol. All fractions were also screened for antidepressant activity at doses of 25 or 50 mg/kg, p.o., upon acute administration in mice.Results: The methanol extract significantly reduced the duration of immobility in FST at dose of 400 mg/kg without affecting locomotor activity in open field test, thus, confirmed its antidepressant activity, which was statistically equivalent to the standard drug (imipramine, 15 mg/kg, i.p.). Ethyl acetate fraction (EAF) exhibited antidepressant activity at 50 mg/kg. Comparative TLC fingerprint studies confirmed the presence of quercetin in methanol extract and EAF. Quercetin was used as a chemical marker to standardize C. indica aerial parts using the validated TLC densitometric method, and the content of quercetin was found to be 0.00172% w/w.Conclusions: The present studies scientifically validated traditional claims of C. indica for antidepressant activity.

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice

Perilla frutescens (Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens (EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress (CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF (3, 6, and 9 mg·kg−1) and a positive control drug fluoxetine (20 mg·kg−1) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test (TST), and forced swimming test (FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in mouse hippocampus were determined by HPLC–ECD. Serum interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects.

GLP-1 receptor agonist liraglutide reverses long-term atypical antipsychotic treatment associated behavioral depression and metabolic abnormalities in rats.

Mood disorder patients that are on long-term atypical antipsychotics treatment frequently experience metabolic dysfunctions. In addition to this, accumulating evidences points to increased risk of structural abnormalities, brain volume changes, altered neuroplasticity and behavioral depression with long-term antipsychotics use. However, there is paucity of preclinical evidences for long-term antipsychotic associated depression-like behavior. The objectives of the present study were: (1) to evaluate influence of long-term antipsychotic (olanzapine) treatment on rat behavior in forced swim test (FST) as a model for depression and; (2) to examine impact of glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide - an antidiabetic medication for type II diabetes, on long-term olanzapine associated metabolic and behavioral changes in rats. Daily olanzapine treatment (0.5 mg/kg; p.o.) for 8-9 weeks significantly increased body weights, food and water intake, plasma cholesterol and triglycerides and immobility time in FST with parallel reduction in plasma HDL cholesterol levels. These results points to development of metabolic abnormalities and depression-like behavior with long-term olanzapine treatment. Acute liraglutide (50 μg/kg; i.p.) and imipramine (10 mg/kg, i. p.) treatment per se significantly decreased duration of immobility in FST compared to vehicle treated rats. Additionally, 3-week liraglutide treatment (50 μg/kg; i.p., daily) partially reversed metabolic abnormalities and depression-like behavior with long-term olanzapine-treatment in rats. None of these treatment regimens affected locomotor behavior of rats. In summary, add-on GLP-1 receptor agonists promise novel alternatives to counteract long-term antipsychotics associated behavioral and metabolic complications.

Effect of microinjecting of 5-aza-2-deoxycytidine into ventrolateral orbital cortex on depressive-like behavior in rats

DNA methylation and histone modification are two major epigenetic mechanisms involved in the pathophysiology of major depressive disorder (MDD) and the action of antidepressants. We and others have recently shown that epigenetic regulation through histone acetylation within ventrolateral orbital cortex (VLO) contributes to the antidepressant-like effects of histone deacetylase inhibitors [HDACi, such as valproic acid (VPA) and MS-275] observed in rats. However, there is so far no investigation focused on the effect of DNA methylation in VLO on depressive-like behaviors. Here, we examined the effects of the DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-aza) on rat forced swimming test (FST) and locomotor activity when microinjected into VLO. We found that bilateral intra-VLO injections of 5-aza increased the duration of immobility in FST in a dose-dependent manner compared to vehicle-treated controls. The effects of 5-aza observed in the FST paradigms could not be attributed to non-specific decreases in activity since the inhibition of DNA methylation in VLO did not cause general impairment in locomotor activity. These results add to the evidence that DNA hypomethylation in VLO is involved in regulating depressive-like behaviors, and suggest that the effect of DNA methylation on depressive-like behaviors appear to be brain region-dependent.