Despair Swim Test Research Articles

Bee venom ameliorates oxidative stress and histopathological changes of hippocampus, liver and testis during status epileptics

The unrelenting progression of neurodegenerative diseases has a negative impact on affected individuals, their families, and society. Recurrent epileptic seizures are the hallmark of epilepsy, and treating it effectively remains difficult. Clarify and understanding effects of the antiepileptic drugs (AEDs) in epilepsy by comparing the therapeutic effects between rats receiving valproic acid (VPA) and Bee venom (BV) was aimed throughout the present study. Four male Wistar rat groups were included: control, epileptic group receiving pilocarpine (PILO), epileptic group treated with VPA and BV respectively. Cognitive functions were assessed by evaluating latency time in hot plate, despair swim test, grooming, rearing and ambulation frequency in the open field. BV has ameliorative effect on electrolytes balancing, assured by decreasing lipid peroxidation, nitric oxide and increasing catalase, superoxide dismutase and glutathione peroxidase activities. BV enhanced restoration of liver functions indicated by alanine transaminase (ALT) and aspartate transaminase (AST), total proteins, and albumin; hormonal parameters total and free testosterone, follicle stimulating hormone (FSH) and Luteinizing hormone (LH) were preserved by BV with great recovery of hippocampus, liver and testicular histopathology and ultrastructure comparing with the epileptic rats. The present findings suggested that BV and its active components offer fresh options for controlling epilepsy and prospective methods via minimize or manage the severe consequences.

Evaluation of Antidepressant activity of Tricholepis glaberrima DC using various Paradigms

In the present experiment, Tricholepis glaberrima DC has been taken to study its antidepressant activity. The study was carried out in two different doses of the test drug. The animals were divided into 4 groups of 5 animals each, respectively. Mice in Group I (control) and II (standard) were administered distilled water, per oral and Imipramine 10mg/kg, per oral once respectively. Group III and IV were treated with the test drug METG in the dose of 100mg/kg and 300mg/kg, respectively. Findings of the test groups were compared with that of standard as well as plain control groups. In despair swim test and Tail suspension method, METG (100mg/kg and 300mg/kg per oral) depicted significant (*p<0.05 and p<0.01) results, in a dose dependent manner, when compared to vehicle treated group, indicating significant antidepressant activity. The results obtained in the present study for antioxidant activity indicate that the plants of Tricholepis glaberrima DC are a significant source of natural antioxidants. This test reveals the antidepressant activity of Tricholepis glaberrima DC Via serotonergic, adrenergic mechanism in a dose dependent pattern.

Evaluation of Antidepressant and Anxiolytic Activity of Fruit Extract of Hylocereus undatus in Experimental Animals

Hylocereus undatus, generally known as dragon fruit was used in the present study to investigate antidepressant and anti-anxiety activity. In antidepressant activity we found that administration of 200 mg/kg and 400 mg/kg ethanolic fruit extract of Hylocereus undatus (EFEHU) and standard drug imipramine (20 mg/kg) for 21 days to respective group of animals they showed significantly reduced the immobility time in both Tail suspension test (TST) and Despair swim test (DST) in dose dependent manner as well as biochemical estimation was done. In anxiolytic activity administration of 200 mg/kg and 400 mg/kg EFEHU and standard drug diazepam (2 mg/kg) for 14 days to respective group of animals. In Elevated plus maze test (EPMT) significantly increased time spent in open arm and number of entries in open arm. The significantly increased level of 5-HT and GABA in brain of mice in dose dependent manner in both DST and EPMT. The phytochemical study of EFEHU showed the presence of alkaloids, tannins, carbohydrates, flavonoids, terpenoids, saponins, oils, phenolic compounds and qualitative examination by HPTLC technique showed that presence of quercetin and gallic acid. Therefore, the presence of such compounds in the extract may be responsible for the antidepressant and anxiolytic activity. Therefore, present study validates its antidepressant and anxiolytic activity. Further, research is required to elucidate its specific mechanism of action and isolation of responsible active principles.

Anti-depressant, Anxiolytic, and the Muscle Relaxant Activity of Hydroalcoholic Extract of Cissampelos pareira Linn. Leaves.

The ethnopharmacological relevance suggests that the ethnic minorities of India use leaves of Cissampelos pareira L. as a traditional medicine for curing various psychopharmacological disorders. To evaluate anti-depressant, anxiolytic, and muscle relaxant activity of hydro-alcoholic extract of Cissampelos pareira. Leaves of Cissampelos pareira were extracted using a hydro-alcoholic solvent. The safety of hydro-alcoholic extract of Cissampelos pareira was assessed by acute oral toxicity (OECD 423). The anti-depressant activity was measured using open field test, locomotor test, despair swim test, tail suspension test. The anxiolytic activity was assessed using elevated plus maze and hole board test, and skeletal muscle relaxant activity was assessed using rotarod, grip strength, chimney, and inclined plane test. No moribund status or mortality was observed in experimental mice up to 2000 mg/kg dose of Cissampelos pareira hydro-alcoholic extract (CPHE). In the open field and actophotometer tests, CPHE 200 and 400 mg/kg treated mice significantly abridged ambulation, number of central squares crossed, total locomotion, and depicted less coordinated movements, and in despair swim and tail suspension tests, CPHE 400 mg/kg treated mice significantly decreased duration of immobility and increased number of climbing, confirming its anti-depressant effect. In an elevated plus-maze test, CPHE 200 and 400 mg/kg increased the open arm exploration, while in the hole board test, CPHE 400 mg/kg treated rats augmented the number of head dips, depicting its anxiolytic effect. In rotarod, grip strength, and inclined plane test, CPHE 400 mg/kg treated mice decreased the fall-off time on a rotating rod, suspended wire, or inclined plane. Furthermore, in the chimney test, treatment with CPHE 400 depicted less coordinated movements in mice; the mice of this group took more time to leave the cylinder, depicting its skeletal muscle relaxant effect. Based on the results, of this study, it can be concluded that CPHE 400 mg/kg exhibits strong anti-depressant, anxiolytic, and muscle relaxant effects, justifying its traditional uses.

Anti-obesity potential of almond (Prunus dulcis) in experimental animals under cafeteria and atherogenic diets.

Background & objectivesNatural dietary supplements are progressively getting famous to supplant synthetic substances particularly in chronic morbidities. The aim of this study was to evaluate the anti-obesity potential of almond on the normal, Cafeteria, and Atherogenic diets.Materials and methodsParameters such as change in body weight, body temperature, lipid profile, organ weights, and fat pad weights were assessed. Central Nervous System related studies (Despair Swim test and Elevated Plus maze test) were also performed to comprehend the effect of the diets, and almond on the brain. All of the experimental animals were randomly assigned to one of three diet categoriesregular, cafeteria, or atherogenic, and fed those diets for 40 days. Each diet had the control group, standard drug group and three almond groups (low dose: 50; medium dose: 100 and high dose: 200 mg/kg body weight). Body weight was recorded every alternate day. On 40th day, body temperature was measured. On day 41, lipid parameters, organ weights, fat pad weights and the CNS parameters were evaluated. ANOVA followed by Duncans Multiple Range Test were used for statistical analysis.ResultsTreatment of animals with either a low or high dose of almond as well as a standard herb prevented a rise in body weight significantly (p = 0.01) in all three diet groups. When a regular diet was replaced with a cafeteria and atherogenic diet, the serum levels of triglycerides and LDL increased significantly, while HDL levels decreased significantly. Overall, almond preparation reduced lipid parameters, organ weights, fat-pad weights, and stabilized CNS parameters substantially.Interpretation & conclusionThe almond high dose was the most effective of all the almond preparations. Our study suggests that chronic administration of almond independently reduces the body weight in experimental animals.

Synthesis and pharmacological evaluation of 3-[5-(aryl-[1,3,4]oxadiazole-2-yl]-piperidine derivatives as anticonvulsant and antidepressant agents

In the present study, we have synthesized a series of fifteen nipecotic acid 1,3,4-oxadiazole based hybrids with significant (60–78%) yields. All the compounds were characterized by using different spectroanalytical techniques such as FT-IR, 1H NMR, 13C NMR, and elemental analysis. This design strategy was validated by using in vivo anti-epileptic and anti-depressant bioassay models. Anti-convulsant activity was evaluated using subcutaneous pentylenetetrazol (scPTZ) in mice and MES induced seizure. Among a spectrum of activities, three compounds (4i, 4m, and 4n) displayed significant activity against pentylenetetrazole (scPTZ) induced seizures. No disruptions in motor co-ordination were observed in mice pretreated with the test compounds in the rotarod test. Their influence on the safety profile of elevated serum levels of biochemical markers such as hepatic and renal toxicity has been found to be safe. The derivatives also show marked anti-depressant activity, devoid of serotonergic augmentation as assessed using the despair swim test, 5-hydroxytryptophan (5-HTP)-induced head twitch test and learned helplessness test. In silico docking studies targeted on homology modelled GABA transporter 1 (GAT1) protein shows the critical enzyme-ligand interactions leading to the inhibition of the GAT1 transporter. The compound 4m was found to be the most active compound among all the synthesized compounds.

Antidepressant in animal models of depression and study of cognitive property

Depression characterized by significant depression of mood and impairment of function. In whole study evaluate the antidepressant activity of ethanolic extract of Bacopa monnieri Linn, to assess the pharmacodynamic interaction of drug with standard nootropic antidepressant, determine effect of drug alone and in combination with standard anti-depressant in brain on amino acid neurotransmitter and acetylcholine esterase activity. Despair Swim test and tail suspension test study of interaction of ethanolic extract Bacopa monnieri with standard antidepressant drug extract used in FST and TST studied. Final perception was GABAmimetic Bacopa monneri decrease the immobility in forced swim test found that GABAergic activity lower in depressed state than normal brain. The control group in both FST and TST. GABA level found decrease than basal values. From experimental evidence it may conclude that ethanolic extract of Bacopa monnieri Linn possesses significant antidepressant activity.

Ameliorative effect of Xiaoyao-jieyu-san on post-stroke depression and its potential mechanisms.

A stroke is a severe life-threatening disease with high fatality and disability rate. This investigation aimed to study the effect of Xiaoyao-jieyu-san (XYJY) on post-stroke depression (PSD) and its potential mechanisms. PSD rats were prepared using middle cerebral artery embolization (MCAO) and chronic unpredictable mild stress (CUMS), and divided into six groups (n = 10)-sham; MCAO; MCAO + CUMS (PSD); PSD + fluoxetine (1.84mg/kg/day, 4weeks); and PSD + XYJY (450mg/kg/day and 900mg/kg/day, 4weeks). Body weight recording, despair swimming test, and sucrose preference test were performed at 0, 3 and 7weeks. Histopathological examination and levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in ventral tegmental area-nucleus accumbens (VTA-NAc) tissue were determined at the end of a 7-week period. Real-time polymerase chain reaction PCR was used to determine mRNA expression of 5-HT1AR and 5-HT2AR, and Western blot was performed to determine expression of BDNF, corticotrophin-releasing factor (CRF), and cannabinoid receptors (CB1R and CB2R) in VTA-NAc tissue. High-performance liquid chromatography coupled with electrospray mass spectroscopy revealed that the constituents of XYJY are mainly paeoniflorin, imperatorin, naringin, arnesene, 2,3,5,4'-tetrahydroxyl-diphenylethylene-2-O-glucoside, kaempferol-3-O-rutinoside, quercetin, hesperidin, cycloastragenol and atractylenolide III. XYJY (900mg/kg) increased the body weight of PSD rats, while XYJY (450mg/kg and 900mg/kg) shortened the duration of immobility and enhanced the sucrose preference of PSD rats. XYJY (450mg/kg and 900mg/kg) increased the levels of 5-HT, NE and BNDF, up-regulated mRNA expression of 5-HT1AR, down-regulated 5-HT2AR, and up-regulated BNDF, CB1R, and CB2R expression in the VTA-NAc tissue of PSD rats but down-regulated CRF. Collectively, the present findings suggested that XYJY has an ameliorative effect on PSD in rats via modulation of BNDF, cannabinoid receptors and CRF in VTA-NAc tissue.

Neuropharmacological Profile of Fractions of Actaea acuminata H. Hara Roots

The methanol extract of Actaea acuminata roots have been previously reported to exhibit significant antianxiety, anticonvulsant and antidepressant activities. In present study fractionation of crude bioactive methanol extract was carried out using different solvents employing standard procedure. Various fractions were evaluated for antianxiety, anticonvulsant and antidepressant activities using elevated plus maze model (EPM), maximal electroshock-induced convulsions model (MES) and forced / despair swim test (FST) respectively. Successive partitioning of bioactive methanol extract was done with ethyl acetate and 1-butanol. The ethyl acetate fraction (EAF; 100 mg/kg), 1-butanol fraction (BF; 25 mg/kg) and remaining methanol extract (RME; 70 mg/kg) were subjected to neuropharmacological activities. The EAF significantly enhanced entries and average time spent in open arms; significantly decreased duration of MES-induced tonic extension phase and significantly decreased duration of immobility time of rats in comparison to control. BF and RME did not exhibit any neuropharmacological activity. Qualitative chemical tests confirmed presence of alkaloids and polyphenols in EAF. It is finally concluded that alkaloids and/or polyphenols are bioactive constituents of A. acuminata which are responsible for neuropharmacological activities.

Role of Glutamate in the Development of Depression in Asthma: A Preliminary Study

The present investigation was carried out to find the role of glutamate in development of depression in asthma using mice. Female albino mice were divided into five groups, group I- normal control, group II- depression, group III- asthma, group IV- asthma+depression and group V- memantine-treated asthma+depression. Various respiratory parameters, histopathology of lungs, forced swim test, sucrose preference test and brain neurotransmitter levels were measured. A significant decrease in tidal volume and air flow rate as well as increase in respiratory rate was found in depression asthmatic group as compared to only asthmatic group, only depression group and normal control group. These same animals when subjected to despair swim test and sucrose preference test, the immobility time was significantly increased whereas preference to the sucrose solution was significantly decreased. Glutamate, 5-HT and norepinephrine levels were significantly increased and dopamine level significantly decreased in depression group and depression along with asthma group as compared to normal control group or asthma group. Treatment with memantine showed improvement in the respiratory parameters and depression parameters as compared to untreated asthmatic mice with depression. Moreover, a positive correlation was observed between airflow rate and immobility. Also, a direct correlation was observed between brain glutamate level and airflow rate as well as brain glutamate level and immobility. These results suggested that glutamate might be the key mediator involved in development of depression in asthma.

Design, synthesis, characterization, and molecular modeling studies of novel oxadiazole derivatives of nipecotic acid as potential anticonvulsant and antidepressant agents

A series of fifteen novel nipecotic acid 1,3,4-oxadiazole hybrids were synthesized with the intent to improve the lipophilicity of nipecotic acid and its penetration through the blood—brain barrier (BBB). The structures of the compounds were established by FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. The effect of the synthesized compounds was assessed on motor coordination using the rotarod test in mice. Anticonvulsant activity was evaluated using the subcutaneous pentylenetetrazol (scPTZ) test in mice. Five compounds (5d, 5e, 5g, 5m, and 5o) exhibited significant protection against scPTZ-induced seizures. None of the compounds produced any disruption in motor coordination as observed in the rota-rod test, nor did they elevate the serum levels of biochemical markers related to hepatic and renal toxicity, affirming their relative safety. The derivatives also exhibited significant antidepressant activity, devoid of serotonergic augmentation as assessed using the despair swim test, 5-hydroxytryptophan (5-HTP)-induced head twitch test and learned helplessness test. In in silico docking studies on a homology model on target GABA transporter 1 (GAT1) protein and the most active compound 5e helped to identify critical enzyme-ligand interactions leading to the inhibition of the GAT1 transporter.

Improvement of Antioxidant Defences and Mood Status by Oral GABA Tea Administration in a Mouse Model of Post-Stroke Depression.

Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation. Methods: Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo. Results: GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity. Conclusions: Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD.

Synthesis and Evaluation of Phenothiazine derivative for Anti-depressant activity

This study was designed to synthesize, characterize and to evaluate the pharmacological activity of substituted phenothiazine derivatives. Totally thirteen compounds, were synthesized by conventional method. Purity of the synthesized compounds was ascertained by TLC and melting point determination by open capillary tube method and they were characterized by IR and NMR spectroscopic methods. Antidepressant activity of all the synthesized compounds was evaluated by despair swim test by using Sprague Dawley Rats. Standard drug Imipramine was used as the control. In the results of the spectral study. all the compounds showed characteristic peak in IR and NMR spectroscopy. In the despair swim test, all the synthesized derivatives showed antidepressant activity. Among them three Compounds (A1, A3 A6 and A8) showed significant antidepressant activity comparing with control drug imipramine. These results are useful for the further investigation in the future.

Design, synthesis and evaluation of acute toxicity studies and anti-depressant activities of some new derivatives of 1, 3-benzoxazin- 4-one

This study was designed to synthesize, characterize and to evaluate the pharmacological activity of 1, 3-benzoxazin- 4-one derivatives. Totally thirteen compounds, were synthesized by conventional method. Purity of the synthesized compounds was ascertained by TLC and melting point determination by open capillary tube method and they were characterized by IR and NMR spectroscopic methods. Antidepressant activity of all the synthesized compounds was evaluated by despair swim test by using Sprague Dawley Rats. Standard drug Imipramine was used as the control. In the results of the spectral study, all the compounds showed characteristic peak in IR and NMR spectroscopy. In the despair swim test, all the synthesized derivatives showed antidepressant activity. Among them three Compounds (A 4 , A 5 and A 7 ) showed significant antidepressant activity comparing with control drug imipramine. These results are useful for the further investigation in the future.

Design, synthesis and Anti-depressant activity of some novel derivatives of Benzothiazepine

Antidepressants are the drugs used to treat depression thereby elevates mood and modifies the behavior. The main aims in the development of new antidepressants were greater efficacy, absence of side effects, lack of toxicity in over dose and earlier onset of action. In this study, a series of novel substituted benzothiazepine was synthesized and evaluated for antidepressant-like activity by using or forced swim test (FST). This study was designed to synthesized; identify and antidepressant-like activity of novel derivatives of benzothiazepine. Our synthetic route started from substituted aromatic aldehyde which was reacted with 2-aminothiophenol and ethyl or methyl acetoacetate led to the formation of the title compounds. Total 22 benzothiazepine derivatives were synthesized. All compounds were tested for antidepressant activity by using or forced swim test (FST). All the synthesized compounds were subjected to antidepressant-like activity study on Sprague-Dawley rats by despair swim test. Imipramine was used as standard control. The results showed that all the compounds showed antidepressant activity. Among them two Compounds (A 3 , A 6 ,B 1 B 3 , and B 6 ) showed significant antidepressant-like activity comparing with standard control imipramine. We investigated the importance of functional group substitutions, in the structural framework of the compounds for their antidepressant-like activity. All compounds showed significant antidepressant-like activity at dose (30 mg/kg). Finally, the encouraging result of the antidepressant-like activity displayed by these compounds may be of interest for further structural modifications to the lead compound and next level studies in the hope of finding a new potent antidepressant prescription.

SYNTHESIS, CHARACTERIZATION AND PHARMACOLOGICAL EVALUATION OF STRUCTURALLY RELATED COMPOUNDS OF DIBENZOXEPIN AND DIBENZOTHIEPIN

This study was designed to synthesize, characterize and to evaluate the pharmacological activity of Dibenzoxepin and Dibenzothiepin derivatives. Totally three compounds, two Dibenzoxepin derivatives and one Dibenzothiepin derivative were synthesized by conventional method. Purity of the synthesized compounds was ascertained by TLC and melting point determination by open capillary tube method and they were characterized by IR and NMR spectroscopic methods. Antidepressant activity of all the synthesized compounds was evaluated by despair swim test by using Swiss albino mice. Standard drug Imipramine was used as the control. In the results of the spectral study, all the compounds showed characteristic peak in IR and NMR spectroscopy. In the despair swim test, all the synthesized derivatives showed antidepressant activity. Among them one compound (PC158) showed significant antidepressant activity comparing with control drug imipramine. These results are useful for the further investigation in the future.

Antidepressant effect of linseed oil on various behavioral and pharmacological models of depression in Swiss albino mice

Background: Linum usitatissimum Linn. (Linaceae) commonly known as linseed or flaxseed is known to be the richest plant source for alpha-linoleic acid, an omega-3 fatty acid. Aim: The objective of the present study was to evaluate the oil extracted from Linseed (LO) for anti-depressant activity in mice. Materials and Methods: Healthy male Swiss albino mice were randomly divided into five groups as follows: (i) Control, (ii) LO (4 ml/kg b.w./day), (iii) LO (8 ml/kg/day), (iv) Fish oil (FO) equivalent to 300 mg/kg/day of Docosahexaenoic acid (DHA), and (v) Standard (Imipramine). The antidepressant effect was evaluated using behavioral models like the Despair swim test (DST) and Tail suspension test (TST), and pharmacological models like potentiation of norepinephrine toxicity, 5-hydroxytryptophan potentiation, tetrabenazine antagonism, and apomorphine-induced cage climbing. Fluorimetric estimation of norepinephrine, dopamine, and 5-hydroxytryptophan levels in the brain was also carried out. Results: In case of behavioral models, LO at 0.2 ml/mice/day, significantly reduced the immobilization time. A significant antidepressant activity of LO was found in the pharmacological models. This was confirmed by the elevated levels of norepinephrine and dopamine in the brains of LO-treated animals, as compared to control animals. Conclusion: Linseed oil showed a significant antidepressant effect in various experimental models of depression in Swiss mice, which seemed most likely to be mediated through an interaction with the adrenergic and dopaminergic systems.

Evaluation of the Antipsychotic Effects of 2-(dimethylamino)- and 2-(methylamino)-7H-naphtho[1,2,3-de]quinolin-7-one Derivatives in Experimental Model of Psychosis in Mice

Research into novel therapeutic strategies for schizophrenia with high efficacy and low side effects has been progressed in recent years. In the present study, anti-schizophrenia activities of 2-(dimethylamino)- and 2-(methylamino)- 7H-naphtho[1,2,3-de]quinolin-7-one derivatives (D1-D10) have been evaluated in ketamine-induced experimental schizophrenia model in mice. For this aim, experimental animals was submitted to ketamine intraperitoneal injection at 100 mg/kg/day. Then, D1-D10 were administrated intra-cerebroventricularly to mice and in next step, animals depressive-like behaviors have been examined by despair swimming test. The obtained results demonstrate that 7H-naphtho[1,2,3- de]quinolin-7-one derivatives, specifically D9, reduced depressive-like behaviors via the decrease of the immobility time and the increase of the swim and climb times. Overall, these results showed that these alkaloids have anti-schizophrenia efficacy and due to their low side effects, they can be used as a new strategy for the treatment of depressive symptoms of schizophrenia patients.

Evaluation of safety and efficacy of brain targeted chitosan nanoparticles of minocycline

The aim of present study was to evaluate the antidepressant-like effects of minocycline hydrochloride (MH); enhance this effect using nanoparticulate drug delivery system; and further evaluate their safety by determining maximum tolerated dose (MTD). Pure drug MH, MH loaded nanoparticles (MHNP) and Tween 80® coated MH encapsulated nanoparticles (cMHNP) were explored for antidepressant-like activity in terms of immobility period using despair swim test (DST) and tail suspension test (TST) in mice (dose equivalent to 100mg/kg MH, i.p.). For MTD determination, Wistar rats were treated with gradual increasing doses of MH and cMHNP orally for 28 consecutive days and observed for body weight, weight indices (WI), behavioral, biochemical and histopathological changes until MTD was found. In mice, MH treatment showed antidepressant-like activity and cMHNP treatment significantly improved this effect. On the other hand, no significant effect was observed for MHNP treated group. However, administration of MH in any case did not produce locomotor activation, suggesting that the antidepressant-like effects of MH may not be attributed to the enhanced locomotion. The MTD was found to be 319mg/kg for MH and 350mg/kg for cMHNP (350mg/kg). Thus surface modified nanoparticles (cMHNP) improved the therapeutic efficacy as well as safety of MH.

Bi-3-Azaoxoisoaporphine Derivatives have Antidepressive Properties in a Murine Model of Post Stroke-Depressive Like Behavior

In the present study, three bi-3-azaoxoisoaporphine derivatives were synthesized and intracerebroventricularly administrated to BALB/c mice. The antidepressant actions in stroke-induced depressive like behavior in mice were examined using despair swimming test and tail suspension test. The results reported that bilateral common carotid arteries occlusion caused a significant abnormality of the normal behaviors. Behavioral models demonstrated that synthesized compounds showed antidepressant action. The most antidepressant active compound was DIME2 (4,4'-dimethyl-7H,7'H- [6,6'-bibenzo[e]perimidine]-7,7'-dione), which decreased the immobility time and increased the swimming and climbing times in despair swimming model. DIME2 also showed similar results in decreasing the immobility time in the tail suspension model. In open field tests, DIME2 at 0.1 μg/μl showed a significant activity in the modification of the distance movement and the number and duration of rearing versus bilateral common carotid arteries occlusion (P<0.001). Furthermore, bilateral common carotid arteries occlusion caused a significant increase in the water consumption and significant decreasing in the sucrose consumption which are indicated as a state of anhedonia, a well known common symptom of transient ischemic stroke-induced depressive like behavior, versus normal group (P<0.001). In conclusion, bi- 3-azaoxoisoaporphine derivatives can be considered as antidepressant agents for post stroke-induced depressive like behavior therapy.