Combined Antidepressant Effect of Acetyl-L-Carnitine and Bupropion against Experimental Animal Model

Depression is one of the most common mental diseases characterized by mood disorders affecting around 322 million individuals in the world. Depression is a feeling of inadequacy, dejection, anhedonia, and decreased activity in any action. Previously acetyl-L-carnitine reported beneficial effects on lipid metabolism, neuroprotection, and some types of depression. Therefore, in the present study, we evaluated the combined effect of acetyl-L-carnitine and bupropion against experimental-induced depression. Albino rats were divided into different groups (each group contained six animals). Normal groups received saline (1 mL/kg, i.p.). The standard group received imipramine (20 mg/kg, i.p.). The ALC group received acetyl-L-carnitine (100 mg/kg, i.p.), and the BPR group received bupropion (20 mg/kg, i.p.). T I and T II groups received acetyl-L-carnitine (30 mg/kg, i.p.) + Bupropion (10 mg/kg, i.p.) and acetyl-L-carnitine (80 mg/kg, i.p.) + Bupropion (30 mg/kg, i.p.), respectively. Antidepressant effects were assessed by forced swim test and sucrose preference test. In both models, the combined effect of the drug produced a significant (p < 0.05) antidepressant action as compared to the depression control group. Based on the findings, the combined effect of acetyl-L-carnitine and bupropion had a better therapeutic effect to combat depression as compared to individual treatments.

Evaluation of the anti-depressant potential of metformin in conditioned defeat model in golden Syrian hamsters

Background: Depression is a prevalent mood condition that has an impact on daily functioning. Globally, depression affects 264 million people. The current pharmacotherapy of depression has a lot of shortcomings. Therefore, there is a need to explore newer therapy that alleviate the symptoms of depression. Metformin was found to possess antioxidant potential and hypothesized to decrease the levels of branched-chain amino-acids essential for tryptophan uptake (precursor for serotonin synthesis). The study was designed to validate the efficacy of metformin as an anti-depressant in conditioned defeat model in male golden Syrian hamsters using open field test (OFT), forced swim test (FST) and Serum serotonin levels. Methods: After obtaining IAEC approval, the study was carried out using 8 golden Syrian hamsters each that were randomly assigned to four groups. The disease control group received 1mL normal saline, positive control was given fluoxetine 12 mg/kg, two groups of metformin 240 mg/kg given pre-insult and post-insult. The variables assessed on every third day included OFT and FST. Following the behavioral tests, serotonin-ELISA was done. To analyse the outcomes, appropriate statistical tests were applied. Results: On standardization, the model was established to a 16-day model. Further, results highlighted a significant difference in OFT, FST and serotonin levels with the metformin group and fluoxetine compared to disease control (p<0.001). However, no significant difference was observed between the fluoxetine and metformin groups (p>0.05), signifying the comparable results. Conclusions: Metformin (240 mg/kg) alleviated the depressive symptoms by modulating both behavioral and serotonin levels.

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.@*METHODS@#Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.@*RESULTS@#The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01).@*CONCLUSION@#The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Evaluations of antidepressant activity of Punica granatum peel extract in albino mice

Background: Depression is the most common disorder of mental illnesses and affects excess of 10-15% of population. According to the WHO reports, more than 350 million persons suffer from depression all over the world. The aim of present study is to evaluate anti-depressant activity of Punica granatum peel extract (PgPE) in albino mice.Methods: Male albino mice (20-30 g) were used. Animals were divided into 5 groups with 6 animals in each which were subjected to forced swim test. Group 1 is control, group 2 received (standard) imipramine 10 mg/kg, p.o, group 3 (T1) PgPE 50 mg/kg, p.o, group 4 (T2) PgPE 100 mg/kg, p.o, group 5 (T3) PgPE 200 mg/kg, at first animals were forced to swim for 15 min (trained), and the study was performed after 24 hrs. All the animals were treated with individual drug 60 min prior to study, animals were forced to swim for 6 min and the duration of immobility was recorded. The mouse was considered immobile when it floats motionlessly or made only those moments necessary to keep its head above the water surface. The total duration of immobility of each mouse was recorded after the test in each group.Results: The duration of immobility is significantly reduced at PgPE 200 mg/kg and results were analysed by one way analysis of variance (ANOVA).Conclusions: PgPE 200 mg/kg significantly (p<0.05) decreases the duration of immobility in mice.

Does the antidepressant-like effect of mirtazapine and venlafaxine differ between male and female rats? / ¿El efecto de tipo antidepresivo de la mirtazapina y la venlafaxina difiere entre ratas macho y hembra?

Abstract 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.

Resumen Introducción La depresión es un trastorno psiquiátrico que representa un problema de salud mundial. Afecta a cerca de 350 millones de personas, predominantemente mujeres. Sin embargo, algunos reportes indican que su incidencia en hombres está aumentando, por lo que es necesario buscar opciones de tratamiento que sean igualmente efectivas en ambos sexos. Objetivo Analizar si existen diferencias relacionadas con el sexo en el efecto de tipo antidepresivo de la mirtazapina y la venlafaxina, y considerar los posibles mecanismos neuroquímicos involucrados. Método se administraron mirtazapina (40 mg/kg) o venlafaxina (60 mg/kg) en esquema subcrónico a grupos independientes de ratas macho y hembra ovariectomizadas tratadas con estradiol y progesterona. Se evaluaron el efecto tipo antidepresivo y las conductas activas (nado y escalamiento) utilizando la prueba de nado forzado (PNF). Resultados a) tanto la mirtazapina como la venlafaxina redujeron la inmovilidad en la PNF en machos y hembras; b) ambos antidepresivos incrementaron las conductas activas en machos; c) en hembras, la mirtazapina y la venlafaxina produjeron un aumento del nado, pero no modificaron el escalamiento. Discusión y conclusión En machos, los efectos de la mirtazapina y la venlafaxina en la PNF se deben a su acción sobre los sistemas serotonérgico y noradrenérgico; en cambio, en hembras sólo se modifica la conducta de nado, lo que sugiere que el estradiol modula las acciones de ambos antidepresivos sobre el sistema serotoninérgico.

Evaluation of antidepressant activity of hydro-alcoholic extract of rhizomes of Nardostachys jatamansi DC per se and in combination with fluoxetine in wistar albino rats and swiss albino mice

Background: Depression is a common mental disorder results due to deficiency of neurotransmitter in the brain. Various medicinal properties of jatamansi are mentioned in Ayurveda. This study evaluated effect of hydro-alcoholic extract of rhizomes of Nordostachys jatamansi DC per se and in combination with fluoxetine in wistar albino rats and swiss albino mice.Methods: Animals of either sex were selected and randomly divided in test group. Jatamansi extract 10:1 and fluoxetine hydrochloride dissolved in distilled water were used. Animals were tested for forced swimming test, tail suspension test and locomotor after given test drug. Results were compared with control and analysed.Results: Nardostachys jatamansi DC, when given to rats showed dose dependent increase in number of rotation during forced swimming test in rats. During forced swimming test in glass jar statistically significant decrease in immobility was observed. Nardostachys jatamansi DC, when given to mice dose dependent statistically significant decrease in immobility time, swimming time and climbing observed. When given along with combination of fluoxetine it shows statistically significant difference in result, confirmed that it can have synergistic antidepressant activity. When used for locomotor activity in mice none of the test drugs significantly increase or decrease the locomotor activity.Conclusions: Jatamansi showed antidepressant like property in various tests conducted on rats and mice. It showed statistically significant result with increasing dose and had synergic effect when given along with fluoxetine.

Anti-stress activity of Ocimum sanctum and alprazolam in animal models

Background: Stress is the physiological, psychological and behavioral response by individuals when they perceive a lack of equilibrium between the demands placed upon them and their ability to meet those demands, which over a period of time leads to ill health. There are several ways of coping with stress. Some techniques of time management may help a person to control stress.Methods: Forced swim test- mice were randomized into two groups according to the body weights. Each group contains six animals. Each individual animal was allowed to swim inside the jar (25-12-25 cm) containing fresh water up to 15 cm height. Mice were allowed swim for 6 min. After initial struggle to escape the animal became immobile. Total immobility period was measured. Rotarod test- mice were randomized into two groups according to body weights. Each group contains six animals. Rats were placed on the lanes. Latency period was recorded at which each rat falls off the rod.Results: In first experiment, anti-stress activity of Ocimum sanctum in mice was demonstrated by measuring the immobility period during forced swim test and in the second experiment the measurement of the latency period of rats in rotarod apparatus was performed. Both the experimental procedures were compared with standard anti stress drug alprazolam.Conclusions: The present study suggests that Ocimum sanctum possess significant anti stress activity but less when compared to alprazolam.

Antidepressant activity of Trigonella foenum leaves in Wistar albino rats

Background: To evaluate antidepressant activity of ethanolic extract of Trigonella foenum in animal models.Methods: A total of 60 healthy male Wistar albino rats weighing 220-250 grams were used and they were divided into 10 groups of 6 rats in each. First five groups (1st -5th) were evaluated by Forced Swim Test (FST) and remaining by Tail Suspension Test (TST). 1st group (control) received normal saline 10 mg/kg, 2nd group (standard) Imipramine 10 mg/kg and 3rd, 4th and 5th groups (test) respectively received Trigonella foenum leaf ethanolic extract [TFEE] in different doses 100 mg, 200 mg, and 400 mg/kg per orally for 14 days. They were evaluated for antidepressant activity using FST after 60 minutes of drug administration on 14th day. Similarly, remaining five groups (6th to 10th) received the same drugs and evaluated using TST after 60 minutes of drug administration. Duration of immobility was noted for six minutes for each rat.Results: One way ANOVA and Tukey Krammer test were used for statistical analysis. The immobility periods were expressed in mean±SD. The immobility period in FST were 207.16±28.7, 50.08±2.9, 46.14±1.2, 40.5±3.4 and 40.0±3.6 seconds respectively for control, standard and three test groups of TFEE (100/200/400 mg/kg). Similarly, immobility periods of 163.11±31.9, 125.03±11.2, 138.81±16.44, 138.16±12.65, 127.58±4.3 seconds were noted for TST for remaining six groups. It was found that TFEE possess statistically significant (p<0.05) antidepressant activity, as evidenced by decrease in the immobility time in both the tests when compared to control group.Conclusions: Present study results demonstrated that TFEE possess antidepressant property in experimental models of depression.

Comparative Behavioral Correlation of High and Low-Performing Mice in the Forced Swim Test

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy. The forced swim test (FST) has been commonly used to evaluate the “antidepressant” properties of drugs yet the individual difference analysis of this test was left scantly investigated along with the possible connection among other behavioral domains. This study conducted an FST-screening in outbred CD-1 male mice and segregated them into three groups: high performers (HP) or the active swimmers, middle performers (MP), and low performers (LP) or floaters. After which, a series of behavioral experiments were performed to measure their behavioral responses in the open field, elevated plus maze, Y maze, three-chamber social assay, novel object recognition, delay discounting task, and cliff avoidance reaction. The behavioral tests battery revealed that the three groups displayed seemingly correlated differences in locomotor activity and novel object recognition but not in other behaviors. This study suggests that the HP group in FST has higher locomotor activity and novelty-seeking tendencies compared to the other groups. These results may have important implications in creating behavior database in animal models that could be used for predicting interconnections of various behavioral domains, which eventually helps to understand the neurobiological mechanism controlling the behaviors in individual subjects.

Effect of ethanol Adiantum capillus-veneris extract in experimental models of anxiety and depression

Depression is one of the most common psychiatric disorders with a prevalence of 15%-25%. Monoamine aminotransferases, in particular, norepinephrine, serotonin, and dopamine, change in the brain of depressed people. Adiantum capillus-veneris is one of the species of the maidenhair fern genus that have traditionally been used to treat cough, cold symptoms, and local hair loss.In this experimental study, white male rats weighing 250-300 g were assigned to 5 groups of 10 each; group 1: Receiving normal saline; groups 2-4: Receiving A.capillus-veneris extract at 50, 100, and 200 mg/kg, respectively; and group 5: Receiving fluoxetine at 10 mg/kg. Chronic unpredictable stress (CUS) was induced by 3-week exposure to chronic stress. The forced swim test and plus maze were used to assess depression and anxiety, respectively. Malondialdehyde (MDA) levels and antioxidant capacity in the serum and brain were measured. Treatment with A.capillus-veneris extract at 200 mg/kg significantly reduced the duration of immobility. In the group given extract at 200 mg/kg, a significant increase in the number of open arm entries was observed when compared to the control group. A.capillus-veneris extract at 50, 100, and 200 mg/kg resulted in a significant increase in the time spent in the open arm. A.capillus-veneris extract reduced MDA levels and increased antioxidant levels of serum and brain in rat. A.capillus-veneris has significant antidepressant and anti-anxiety effects in rat, probably due to its antioxidant and anti-inflammatory activities.

Evaluation of anti-depressant activity of zinc and vitamin B6 as adjuvants to fluoxetine in an animal model of depression

Background: Depression is a significant public health problem. It is estimated by the World Health Organization that more than 300 million people suffer from depression globally. Micronutrient deficiencies have been constantly linked to depression. The currently used drugs in treatment of depression modulate the excitatory and/or the inhibitory neurotransmission pathways through different mechanisms. The aim of the present study was to compare the antidepressant effect of the micronutrients, zinc and vitamin B6, as adjuvants to Fluoxetine in Albino Wistar rats.Methods: Eighteen albino wistar rats of 180-280grams of either sex were used in the study to evaluate the anti-depressant activity after approval from the Institutional Animal Ethics Committee. They were divided into three groups of six rats each (3 groups). Group 1 was control group which received only distilled water, group 2 was standard group which received fluoxetine and group 3 was test group which received zinc, vitamin B6 and fluoxetine. The anti-depressant activity was measured using the forced swimming test (FST) which works on the principles of behavioral despair. Data analysis was done using IBM SPSS software, version 25.0 and p value <0.05 was considered statistically significant.Results: The rats of the standard and test groups had latency periods’ means of 268.83±30.16, 126.17±22.33 and 125.33±11.86 on 254.83±13.00, 118.67±8.16 and 127.17±6.68 seconds on days 1, 7 and 14 respectively (p <0.001) and the rats of the standard and test groups had despair periods’ means of 177.00±7.46, 95.17±10.65, 93.17±7.47and 167.17±14.82, 97.33±7.63 and 87.50±4.1 seconds on days 1, 7 and 14 respectively (p <0.001).Conclusions: Supplementation of zinc and vitamin B6 to the standard treatment fluoxetine yielded better anti-depressant activity than fluoxetine alone in rats subjected to stress.

Assessment of anti-depressant activity of omega 3 fatty acids in rodents

Background: Depression contributes to significant disease burden at national and global levels. At the personal and domestic level too, depression leads to poor quality of life, causing a huge socioeconomic impact. In the world, over 300 million people are estimated to have depression and the numbers of depressed persons are only projected to go up.Methods: The forced swim test (FST) is one of the most commonly used animal models for assessment of antidepressant effects in rodents. In the modified version of this test, the rats are forced to swim in a glass tank with no means of escape, inducing a behaviour of immobility, which resembles a state of despair, akin to depression in humans. The rats were divided into 6 groups: 1. control group: treated with distilled water; 2. standard group treated with fluoxetine Hcl (10mg/kg); 3.test-1 group treated with omega-3 FAs (300mg/kg); 4.test-2 group treated with a higher dose of omega-3 FAs (500 mg/kg); 5.test-3 group treated with omega-3 FAs (300mg/kg) and fluoxetine (10mg/kg); and 6.test-4 group treated with omega-3 FAs (500 mg/kg) and fluoxetine (10mg/kg).Results: The independent between-groups ANOVA yielded a statistically highly significant result, F (5, 30) = 9.47, P <0.001. Thus, the null hypothesis of no difference between the means was rejected. To further evaluate the nature of the differences between the means of the six groups, the statically significant ANOVA result was followed by Tukey's honest significant difference post-hoc tests.Conclusions: This study finds that omega 3 fatty acids have intrinsic antidepressant activity, and the combination of fluoxetine and omega 3 fatty acids has significantly more antidepressant effect than fluoxetine alone in the forced swim test done on Wistar rats.

The protective effect of L. siceraria against depression using behavioural despair animal models

Background: In recent years, the search for novel pharmacotherapy from medicinal plants for psychiatric illness was significantly progressed. The present study was performed to evaluate the antidepressant activity of ethanolic extract of Lagenaria siceraria in animal models.Methods: The antidepressant activity of ethanolic extract of the fruit of L. siceraria in rats was assessed using forced swim test and tail suspension test. Imipramine at 15 mg/kg was used as standard antidepressant drug.Results: The ethanolic extract of L. siceraria fruit (EELS) was significantly and dose-dependently reduced the duration of immobility after repeated treatment for 7 days in Forced swim test and Tail suspension Test. But combination of L. siceraria (200mg/kg) with Imipramine gave a highly significant result (p<0.001) in reduction of immobility duration and the effect of high dose (400mg/kg) with imipramine (15mg/kg) did not decrease the duration of immobility period in both animal models at end of the study. In this work the dose of 400mg/kg afforded more protection than the imipramine.Conclusions: The results obtained from this study was indicate that the antidepressant activity of L. siseraria.

Antidepressant activity of aqueous extract of Momordica charantia leaves

Background: Depression is a common debilitating illness contributing to increase in morbidity and mortality worldwide. 20% of all depressed patients are refractory to treatment with available antidepressants at adequate doses. Momordica charantia commonly known as Karela is widely used in Indian cuisine. This study was carried out to evaluate its lesser known Antidepressant activity. The objective of this study is to evaluate the Antidepressant activity of Aqueous extract of Momordica charantia leaves.Methods: This study was done in Department of Pharmacology, JNMC, AMU. Tail Suspension test and 5-Hydroxytrytophan induced Head Potentiation was evaluated in Swiss Albino mice. Forced swim test, Learned Helplessness test and Spontaneous motor activity was noted in Albino Wistar rats respectively at doses of AEMC (Aqueous extract of Momordica charantia leaves) 100mg/kg, 200mg/kg and 300mg/kg.Results: AEMC at all three doses 100mg/kg, 200mg/kg and 300mg/kg exhibited antidepressant activity by significantly decreasing the immobility time in Tail Suspension test and except 100mg/kg. In forced swim test psychostimulant activity of AEMC was ruled out in Spontaneous motor activity. Number of Escape failures was decreased in Learned Helplessness test at doses of AEMC 200mg/kg and 300 mg/kg. Increase in Head twitches was seen only with AEMC 300mg/kg in 5-Hydroxytrytophan induced Head Potentiation in mice.Conclusions: Aqueous Extract of Momordica Charantia leaves exhibits Antidepressant activity in animal models of Depression.

The effect of docosahexaenoic acid (DHA) supplementation on experimental depression in mice

Background: Depressive disorder is a prevalent psychiatric disorder, which affects 21% of the world population. Many drugs which are available as effective antidepressants produce various side effects like sedation weight gain postural hypotension etc., so there is need to develop novel compounds with minimized side effects. Hence this study was aimed to investigate the antidepressant activity of DHA, an omega-3 polyunsaturated fatty acid in albino mice.Methods: Animals were divided into four groups, consisting six mice in each group. Out of these, group I served as control (2% gum acacia), group II and III received test drug in two different doses 200mg/kg and 300mg/kg respectively and group IV received fluoxetine (20mg/kg) as standard drug. To determine the antidepressant-like activity, we used forced swim test and tail suspension test in mice. These methods are based on the observation that a mouse show alternating agitation and immobility; the immobility is indicative of a state of depression.Results: DHA produced significant antidepressant effect at all the doses, as indicated by reduction in immobility times as compared to control in both FST and TST. (P?0.05) The efficacy of DHA at dose of 300 mg/kg was comparable with that of fluoxetine. DHA at 200mg/kg dose showed significantly less antidepressant activity compared to fluoxetine. (P?0.05).Conclusions: The result specifies that compared to two doses of DHA (200mg/kg and 300mg/kg), higher dose of DHA found as an effective dose for treating depression produced due to stress.

Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine.

Background: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. Objective: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Materials and Methods: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose‑finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). Results: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic‑serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs. Conclusion: The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential.

Antidepressant activity of Simvastatin in behavioral models of depression in rats.

Background: There is evidence, that statins can augment the antidepressant effects of fluoxetine in rats. Hence the present experimental study was designed to evaluate the effect of Simvastatin on duration of immobility in acute forced swim test (Acute FST) and Chronic forced swim test (Chronic FST), as models of behavioral despair in rats. Methods: In acute FST and Chronic FST models, effects of simvastatin (Smv) and fluoxetine (Flx) per se and in combination, on immobility of rats were compared. Open field test was performed to discriminate between the general behavioral stimulation and antidepressant effect of study drugs. Results: In Acute FST, duration of immobility decreased (171.33 ± 6.15 sec) non-significantly in simvastatin group, & decreased significantly in the groups of rats which received fluoxetine alone (161.33 ± 8.68, P < 0.01) or in combination with simvastatin (167.66 ± 7.71 sec, P < 0.001). The 3 treatment groups did not differ from each other. In chronic FST duration of immobility lowered significantly in both, the fluoxetine treated group (147.66 ± 8.73) and the combination treated group (130.5 ± 5.68 sec) with significant fall in the combination group (P < 0.001) compared to the individual therapy groups. Conclusions: Lowering cholesterol levels with statins not only reduces risks for cardiovascular events, but also affect serotonergic neurotransmission, leading to clinical efficacy of standard antidepressants. Simvastatin can augment the antidepressant effects of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.

Evaluation of antidepressant and analgesic activity of tapentadol with mirtazapine: an experimental study.

Background: Data comparing tapentadol with an antidepressant is limited. A comparison of tapentadol with mirtazapine at different dose has not been performed, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that tapentadol should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a study evaluate antidepressant and analgesic activity of tapentadol with mirtazapine at different doses in Swiss albino mice. Methods: Tapentadol was administered at 10, 20 and 40 mg/kg (i.p) once daily for 14 days to swiss albino mice of either sex. The immobility period for antidepressant activity of mice were recorded in forced swim test and reaction time for analgesic activity of mice were recorded in tail flick test of the control and drug treated group. The antidepressant and analgesic activity of tapentadol (10, 20, 40 mg/kg i.p) was compared with that of mirtazapine (3, 5, 7 mg/kg i.p), administered for 14 days. Results: Tapentadol produced better antidepressant at (20, 40 mg/kg), but less at 10 mg/kg and significant analgesic activity at all the three doses, as indicated by reduction in immobility times and increase in reaction time as compared to control. Mirtazapine produced no antinociceptive activity at 3 mg/kg, but significant at 5, 7 mg/kg and showed better antidepressant activity at all the three doses in mice. The result of this study indicates the better analgesic activity of tapentadol at all the doses and least antidepressant activity at 10 mg/kg, as compared to mirtazapine which has shown better antidepressant activity at all the three doses but no analgesic activity at 3 mg/kg. Conclusion: It can be concluded that tapentadol is a better drug in case of depression associated with pain compared to mirtazapine in mice.

Flavonoid-rich fraction of the Monodora tenuifolia seed extract attenuates behavioural alterations and oxidative damage in forced-swim stressed rats / 中国天然药物

The antidepressant effects of the flavonoid-rich fraction of Monodora tenuifolia seed extract were examined by assessing the extent of attenuation of behavioural alterations and oxidative damage in the rats that were stressed by forced swim test. Compared with the model control group, the altered behavioural parameters were attenuated significantly (P < 0.05) in the group treated with the flavonoid-rich fraction (100 and 200 mg·kg(-1)), comparable to the group treated with the standard drug, fluoxetine (10 mg·kg(-1)). The flavonoid-rich fraction and fluoxetine improved significantly (P < 0.05) the activities of the antioxidant enzymes such as superoxide dismutase and catalase as well as other biochemical parameters such as reduced glutathione, protein, and nitrite in the brain of the stressed rats. These results suggested that the flavonoid-rich fraction of Monodora tenuifolia seed extract exerted the antidepressant-like effects which could be useful in the management of stress induced disease.

Punarnavine, an alkaloid isolated from ethanolic extract of Boerhaavia diffusa Linn. reverses depression-like behaviour in mice subjected to chronic unpredictable mild stress.

Punarnavine (20 and 40 mg/kg) and fluoxetine (20 mg/kg) per se administered orally for 14 successive days significantly decreased immobility periods of both unstressed and stressed mice in forced swim test. These drugs also significantly decreased sucrose preference in both stressed and unstressed mice as compared to their respective controls, indicating significant antidepressant-like activity. The drugs did not show any significant effect on locomotor activity of mice. The alkaloid also significantly decreased monoamine oxidase (MAO-A) activity, malondialdehyde levels in both unstressed and stressed mice; and significantly reversed the stress-induced decrease in reduced glutathione and catalase activity. It also significantly attenuated the stress-induced increase in plasma nitrite and corticosterone levels. Thus, punarnavine showed antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO-A activity, decrease in plasma nitrite levels and due to its antioxidant activity. In addition, punarnavine also showed antidepressant-like activity in stressed mice possibly through decrease in plasma corticosterone levels.