Bupropion and varenicline administration reversed depressive behavior induced by acetamiprid exposure in mice: the role of nAChRs in depression.

Acetamiprid (ACE), is a popular neonicotinoid pesticide, that has a high affinity for mammalian nicotinic acetylcholine receptors (nAChRs). Therefore, ACE might induce depressive effects by perturbing the cholinergic system in mammalian. The aim of this study was to evaluate the effects of ACE exposure on depressive-like behaviors and grip strength (GS) in mice. Also the possible role of nAChR activation in depression was assessed by varenicline, and bupropion. Male Swiss mice (27 ± 2 g) were daily exposed to ACE by gavage (0.1, 1, 5 mg/kg), behavioral tests took place after 3 h, 7 days and 15 days, the subacute ACE (0.1 mg/kg) exposure was assessed after 30 days. Varenicline (0.5 mg/kg) or bupropion (4 mg/kg) were injected intraperitoneally 30 min prior exposure to (1 mg/kg) ACE. The locomotor activity, forced swimming test (FST), and sucrose preference (SP) test were assessed. After a week ACE dose dependently increased the immobility time during FST, and after 15 days' depressive behavior was observed equally for ACE (0.1-5 mg/kg). The subacute exposure (0.1 mg/kg) significantly increased the immobility time, SP also declined that revealed anhedonia. These behavioral changes showed that ACE can initiate depressive effects. The changes in locomotor activity were not significant. GS significantly reduced following a week of exposure to ACE (1-5 mg/kg) that indicated neurotoxicity. These effects were antagonized by bupropion or varenicline, thus ACE effect on nAChRs was essential in initiating the depressive behavior.

Design, synthesis, docking, and antidepressant activity evaluation of isatin derivatives bearing Schiff bases.

Objectives: Depression is a prevalent psychiatric disorder. Treatment of depression is still a challenge due to the lack of response of some patients to a variety of available medications and side effects. Isatin is an interesting molecule with diversified biological effects. It also participates in many synthetic reactions, as a precursor molecule. In this study, a new series of N-alkyl and N-benzyl isatin derivatives bearing Schiff bases were synthesized and screened for antidepressant activities in mice. Materials and Methods: The synthesis was initiated by N-alkylation and N-benzylation of isatin by an alkylation reaction to give N-substituted isatins. 2-(Benzyloxy) benzohydrazide derivatives were synthesized by treating methyl2-hydroxybenzoate with benzyl bromide or 4-chlorobenzyl bromide which was followed by a reaction with hydrazine hydrate to provide acid hydrazide derivatives. The final compounds were obtained by condensation of N-substituted isatins with 2-(benzyloxy) benzohydrazide derivatives as Shiff-base products. Compounds were evaluated for antidepressant activities in mice by the locomotor activity, marble burying test, and forced swimming test. Monoamine oxidase-A (MAO-A) enzyme has been used for molecular docking studies. Results: Compounds 8b and 8e in both doses, and 8 c in the lower dose, reduced immobility time during the forced swimming test relative to the control group. All preparations reduced the number of marbles buried compared with the control group. The highest docking score was -11.01 kcal/mol for compound 8e. Conclusion: N-Benzylated-isatin (8b, 8e) and N- acetic acid ethyl ester -isatin derivatives (8c) showed more effective antidepressant activity compared with N-phenyl acetamide isatin derivatives. Docking results relatively confirm the pharmacological results.

Effects of Asparagus officinalis on immune system mediated EAE model of multiple sclerosis.

Background: About 5 to 10 percent of the population in developed countries are affected by autoimmune diseases. One of the most important autoimmune disease with high prevalence rate is Multiple sclerosis in which there is currently no definitive cure for it, and most medications such as interferons are used only to limit the disease. The present study aims to investigate the effect of using Asparagus Officinalis fractions in an immune system mediated model of multiple sclerosis. Material and Methods: Fractionation was performed by maceration using n-hexane, chloroform, chloroform-methanol (9: 1), n-Butanol and methanol solvents from aerial parts of Asparagus Officinalis. Thin layer chromatography, NMR and phenolic component measurement were done and two fractions were selected for checking in MS induced in vivo model. Results: It was observed that chloroform-methanolic and N-Butanol fractions had higher content of saponin in comparison of other extracts. Also, it was showed that the methanolic and n-Butanol extracts contains the highestportion of glycosylic steroid saponins in comparison to other fractions. Regarding experimental autoimmune encephalomyelitis (EAE) score, Butanolic and methanolic fractions with doses higher that 100mg/kg showed a potent supportive effects as long as locomotor activity protection even in lower dose in comparison to phosphate buffered saline (PBS) group. Conclusion: Considering the proved different effects of saponin compounds on the immune system we observed that those fractions altered the circulatory peripheral blood cells and also remit the clinical signs after EAE induction along with enhanced myelin sheath content in the median region of corpus callusom. It could be inferred that this fractions are promising candidates for further investigation as dose-dependent immune system regulating compounds in multiple sclerosis patients.

Vitamin B6 Antidepressant Effects Are Comparable to Common Antidepressant Drugs in Bacillus-Calmette-Guerin Induced Depression Model in Mice.

Objective: Bacillus-Calmette-Guerin (BCG) inoculation in mice produces an acute period of illness followed by a chronic depressive-like behavior period that lasts for few weeks. The aim was to evaluate vitamin B6 antidepressant effect in comparison with common antidepressants. Method : BCG (0.2 ml/mouse) single dose was intraperitoneally inoculated in male mice. Vitamin B6 (100 mg/kg), fluoxetine, imipramine, or venlafaxine (10 mg/kg each) were intraperitoneally injected for 14 consecutive days following BCG administration. Illness was evaluated following inoculation and depressive-like behaviors were assessed on days 7 and 14. Results: Illness was induced by BCG since mice lost weight and locomotor activity was reduced. Illness was prevented by vitamin B6 similar to antidepressant drugs. Despair was measured by immobility time during the forced swim test and BCG increased it compared to control (193 ± 3s vs 151 ± 7s, P < 0.01) on day 7, and (200 ± 5s vs 147 ± 6s, P < 0.001) on day 14. Vitamin B6, like antidepressants, reduced despair. BCG clearly induced anhedonia evaluated by sucrose preference test (47.5%), and it was soothed by B6 and the antidepressants. Novelty-suppressed feeding test evaluated long term depressive behavior after 14 days. BCG increased the latency to first feeding (222 ± 41s vs control 87 ± 2.6s, P < 0.001) and reduced food consumption per body weight (13 ± 1 mg/g vs control 19 ± 2 mg/g, P < 0.001) while B6 like antidepressants reduced latency and improved food consumption. Conclusion: Vitamin B6 efficiently prevented BCG sickness and depression that was comparable to common antidepressant drugs. Therefore, B6 supplement for preventing depression in high-risk individuals is suggested for further clinical research.

Extraction and Fractionation of the Seaweed Sargassum plagyophylum and Evaluation of Fractions on Depression Induced by Interferon Alpha in Mice.

Background: Marine organisms such as seaweeds, produce potent chemicals with characteristic biological features. Sargassum species have great potential to be used for neuronal protection as part of nutraceuticals. The aim was to investigate the effects of hexane and methanol extracts of Sargassum plagyophylum from the Persian Gulf on depression induced by interferon-α (IFNa) in mice. Materials and Methods: S. plagyophylum was extracted by maceration with methanol-ethyl acetate solvent (1:1). The extract was evaporated and partitioned by hexane and methanol solvents. Male mice were used, depression was induced by SC injecting IFNα (16 × 10 5 IU/kg) for 6 days. Animals were subject to the forced swimming test (FST) after the locomotor test, on day 7. The extracts were administered IP either one single dose (acute) before the test, or simultaneously with IFNα (sub-acute). Results: The locomotor activity was not different from control values. IFNa increased the immobility time during FST (140 ± 14 s vs. control group 95 ± 9 s, P < 0.05). Hexane extract acute (40 mg/kg) injection was not effective while its sub-acute (20 mg/kg) injection reduced immobility time (46 ± 8 s, P < 0.001 vs. IFNa alone). Methanol extract acute (20 mg/kg) and sub-acute (20 mg/kg) administration significantly reduced immobility during the FST (78 ± 20 s, and 72 ± 8 s respectively, P < 0.05 vs. IFNa alone). Conclusion: S. plagyophylum has antidepressant effects, the hexane extract could prevent depression while the methanol extract not only prevented but also treated depression induced by IFNa in mice. Since this species is abundant in the Persian Gulf further clinical studies on its psychological effects are warranted.

Creatine and Alpha-Lipoic Acid Antidepressant-Like Effect Following Cyclosporine A Administration

Objectives: Cyclosporine A (CYA), is an immunosuppressant drug used to prevent graft rejection, but it may initiate neuropsychological problems such as depression. The aim was to evaluate the antidepressant-like effects of creatine (Crt), a mediator of oxidative phosphorylation, and alpha-lipoic acid (ALA), a cofactor for the mitochondrial respiratory chain following CYA administration. Materials and Methods: Female mice (27 ± 2 g) were used, immobility time during the forced swimming test (FST) was measured, and hippocampal brain-derived neurotrophic factor (BDNF) level was evaluated. CYA 20 mg/kg, ALA 40 mg/kg, fluoxetine 20 mg/kg, and Crt 10 mg/kg (oral) were administered for 6 consecutive days, and the tests were performed on day 7. Results: ALA, but not Crt, treatment alone decreased immobility in the FST (i.e., decreases depression-like behavior). CYA administration increased immobility in the FST (175.1 ± 13.16 s, vs. vehicle 130.9 ± 13.5 s, p= 0.0364), and this depression-like behavior was prevented by co-administrating, ALA (100 ± 15.9 s, p= 0.020) or Crt (93.5 ± 16.6, p= 0.009) and the positive control, fluoxetine. Notably, there was a synergistic effect of Crt-ALA co-administration since CYA-induced immobility was lower in this group than in the groups pretreated with Crt or ALA. These behavioral changes were observed without treatment effects on locomotor activity in an open field. CYA treatment increased hippocampal BDNF protein levels prevented by co-administration of ALA (with or without Crt) or fluoxetine. Conclusion: CYA-induced depression-like behavior might be related to hippocampal mitochondrial dysfunction as ALA and Crt prevented the development of this behavioral phenotype. ALA, similar to fluoxetine, prevented BDNF alteration and its possible neurological changes.

In vitro and in vivo evaluation of an ionic sensitive in situ gel containing nanotransfersomes for aripiprazole nasal delivery.

In the current study, a composite in-situ gel formulation containing aripiprazole (APZ) loaded transfersomes (TFS) was developed for the intranasal brain targeting of APZ. APZ loaded TFS were prepared by applying the film hydration method and optimized using an irregular factorial design. The prepared formulations were optimized based on different parameters including particle size, polydispersity index (PdI), zeta potential, encapsulation efficiency (EE) and release efficiency (RE). The optimized APZ-TFS were distributed in an ion-triggered deacetylated gellan gum solution (APZ-TFS-Gel) and evaluated in terms of pH, gelling time, rheological properties and in-vitro release study. The therapeutic efficacy of the best APZ-TFS-Gel was then tested in the mice model of schizophrenia induced by ketamine by evaluating various behavioral parameters. The optimized formulation showed the particle size of 72.12 ± 0.72 nm, the PdI of 0.19 ± 0.07, the zeta potential of -55.56 ± 1.9 mV, the EE of 97.06 ± 0.10%, and the RE of 70.84 ± 1.54%. The in-vivo results showed that compared with the other treatment groups, there was a considerable increase in swimming and climbing time and a decrease in locomotors activity and immobility time in the group receiving APZ-TFS-Gel. Thus, APZ-TFS-Gel was found to have desirable characteristics for therapeutic improvement.

AChR is partly responsible in mice depressive-like behavior after Phosalone exposure.

BACKGROUND: Phosalone (Pln) is an organophosphorus pesticide acetylcholinesterase (AChE) inhibitor. Blockade of AChE amplifies ACh signaling that is related to depressive symptoms. The effects of Pln exposure were evaluated on depressive behavior in mice and the involvement of muscarinic ACh receptor (MAChR) was assessed. MATERIAL AND METHODS: After measuring total activity in the locomotor test the immobility time during the forced swimming test (FST) in male mice was evaluated as an index of depression. Pln single dose was administered by gavage feeding and examined after 3 h (day1) and on day 7 for evaluating delayed toxicity. In separate groups Pln was administered for 5 consecutive days and examined on day 6 also after one-week delay on day12. RESULTS: While there were only marginal differences in the locomotor tests. Immobility time during the FST significantly increased on day1 by Pln 6, 12, 40 mg/kg (185 ±â€¯17 s, 186 ±â€¯9 s, 172.0 ±â€¯7 s respectively) compared with control animals (149 ±â€¯8 s, p < 0.01), immobility time was higher than control on day 6 after multiple exposures to Pln (0.6, 6, 12, 20 mg/kg 190 ±â€¯20s, 210 ±â€¯4 s, 196 ±â€¯10s, 204 ±â€¯9 respectively, vs control 153 ±â€¯7 p < 0.001). The immobility time remained high following a week of relapse. The co-administration of Pln with scopolamine (Scp) a MAChR antagonist reduced immobility time (141 ±â€¯10s vs Pln 186 ±â€¯9 s, p < 0.01). CONCLUSION: Single exposure to Pln induced depressive-like effects that were reversed by Scp, indicating that MAChR stimulation may be involved. While cumulative exposures caused more pronounced changes in depressive behavior that remained after a week from the last exposure.

A Synbiotic Mixture Ameliorates Depressive Behavior Induced by Dexamethasone or Water Avoidance Stress in a Mouse Model.

OBJECTIVES: Disruption of the hypothalamic-pituitary-adrenal axis by stress and glucocorticoid drugs is a major cause of depression. The benefits of probiotics may extend to systems beyond the gastrointestinal tract, i.e., the central nervous system. Therefore, the effect of a synbiotic (probiotic + prebiotic) mixture on dexamethasone (Dex) and stress-induced depression was investigated. MATERIALS AND METHODS: Male albino mice were used, the forced swimming test (FST) measured despair, and the sucrose preference test measured anhedonia. The synbiotic regimen (12.5x106 CFU) was supplemented in drinking water for 7 days. Dex was administered subcutaneously either in a single dose on the test day or for 7 days. Water avoidance stress (WAS) was induced for 1 hour each day for 4 days. RESULTS: Drinking the synbiotic reduced immobility time during the FST (54±7 sec vs. 111±6 sec in the control water group, p<0.001). Dex injection significantly increased the immobility time (single dose: 166±6 sec and 7 days: 174±9 sec) compared with the control groups, while adding the synbiotic to their drinking water reduced it (single dose: 81±6.6 sec, and 7 days: 84±14 sec), indicating that the synbiotic reversed Dex-induced depression. WAS increased the immobility time (148±11 sec vs. sham 99±6 sec, p<0.001) in the FST test. When the synbiotic treatment was added following WAS, the immobility time decreased (81±6.5 sec). The synbiotic groups also had a higher sucrose preference percentage. CONCLUSION: The synbiotic mixture prevented the effects of WAS, acute or sub-acute Dex-induced depression in mice. Therefore, probiotics might be useful and safe supplements to prevent depression related to stress or glucocorticoid therapies, a phenomenon that deserves further evaluation.

A Synbiotic Mixture Augmented the Efficacy of Doxepin, Venlafaxine, and Fluvoxamine in a Mouse Model of Depression.

OBJECTIVES: Currently available antidepressant drugs have notable downsides; in addition to their side effects and slow onset of action their moderate efficacy in some individuals may influence compliance. Previous literature has shown that probiotics may have antidepressant effects. Introducing complementary medicine in order to augment the efficacy of therapeutic doses of antidepressant drugs appears to be very important. Therefore, the effect of adding a synbiotic mixture to drinking water was assessed in a mouse model of depression following the administration of three antidepressant drugs belonging to different classes. MATERIALS AND METHODS: The marble burying test (MBT) and forced swimming test (FST) were used as animal models of obsessive behavior and despair. The synbiotic mixture was administered to the mice's drinking water (6.25x106 CFU) for 14 days and the tests were performed 30 min after the injection of the lowest dose of doxepin (1 mg/kg), venlafaxine (15 mg/kg), and fluvoxamine (15 mg/kg) on days 7 and 14. RESULTS: After 7 days of ingestion of the synbiotic mixture, immobility time decreased in the FST for doxepin (92±5.5 s) and venlafaxine (17.3±2.5 s) compared to the control group (drinking water), but fluvoxamine decreased immobility time after 14 days of ingestion of the synbiotic mixture (70±7.5 s). Preadministration of the synbiotic mixture improved the MBT test response for venlafaxine, while it did not change the results for the other two drugs. CONCLUSION: Adding the synbiotic mixture to drinking water improved the efficacy of discrete antidepressant drugs particularly during the FST. Probiotics could be a useful complementary medicine for drug-resistant depressed individuals.

Dextromethorphan improved cyclosporine-induced depression in mice model of despair.

BACKGROUND AND PURPOSE: Cyclosporine (Cyc) is a calcineurin inhibitor used in immunosuppressive therapy that may cause psychological problems such as depression. Previous investigations have shown the positive antidepressant effects of dextromethorphan (Dxt). Therefore, the aim of this study was the evaluation of the Dxt effect on Cyc-induced depression in an animal model of despair in two separate cohorts. EXPERIMENTAL APPROACH: Male albino mice were used, first total activity was evaluated by the locomotor test, and then after that, the immobility time during the forced swimming test was measured as an indicator of depression. Cyc, Dxt, and fluoxetine (the reference antidepressant drug) were all administered IP. Tests were performed either 4 h after injection (cohort 4 h) or in separate groups 24 h after injection (cohort 24 h). FINDINGS/RESULTS: Cyc reduced total activity measured after 4 h in the locomotor test and it was normalized after 24 h. Immobility time dose-dependently increased during the forced swimming test and remained so after 24 h (cohort 24 h; Cyc 10, 20, and 40 mg/kg, 157 ± 22, 180 ± 8, and 228 ± 4 s, respectively; Cyc 40 mg/kg P < 0.001 vs control 142 ± 13 s) that indicated Cyc induced depressive-like behavior. Dxt (30 mg/kg) like fluoxetine reduced the immobility time when co-administered with Cyc compared with Cyc and remained effective after 24 h (cohort 24 h; 120 ± 30, P < 0.001 vs Cyc 40 mg/kg alone). CONCLUSION AND IMPLICATIONS: Dxt was a useful drug for preventing Cyc-induced depression that remained effective for 24 h in mice. Since interpretation from animal studies to humans must be done with caution further clinical studies on the effect of Dxt in patients suffering from psychological side effects of Cyc may be reasonable.

Celecoxib, ibuprofen, and indomethacin alleviate depression-like behavior induced by interferon-alfa in mice.

Background Interferon-α (IFNα) therapy causes psychiatric side effects, including depression that may result in poor compliance of therapy. It is important to find alternative therapies for the prevention of IFNα induced depression. Non-steroidal anti-inflammatory drugs (NSAIDs) have been useful in depressive disorder. Therefore the effects of celecoxib, ibuprofen, and indomethacin were evaluated following IFNα-induced depression in mice. Methods Male albino mice weighing 26 ± 2 g were used. Depression was induced by IFNα (16 × 105 IU/kg, SC) for six consecutive days. Animals were first subject to the locomotor test, then the splash test and finally the forced swimming test (FST) on the 7th day. The NSAIDs were administered (IP) either one single dose before the test, or simultaneously with IFNα. Results locomotor activity was only impaired by ibuprofen high dose (75 mg/kg), thus it was not further evaluated. Following IFNα therapy depression-like behaviors were observed; significant changes during the splash test (grooming time 24 ± 7 sec vs. control 63 ± 7 sec), the FST (immobility time 166  ± 15 sec vs. control 128  ± 6 sec), and sucrose preference reduced to 64 ± 0.8%. The NSAIDs noticeably reduced the immobility time in FST, while grooming time was increased. Celecoxib and indomethacin single doses were effective while ibuprofen showed better antidepressant effects when it was administered along with IFNα. Conclusions The NSAIDs were able to prevent IFNα induced depression in mice. NSAIDs administration with IFNα does not interfere with clinical benefit effects of IFNα and they could also be useful to prevent IFNα psychiatric side effects, thus further clinical trials are suggested.

The effect of different partitions of seaweed Sargassum plagyophylum on depression behavior in mice model of despair.

Background Seaweeds are a famous traditional food resource in some countries containing different types of secondary metabolites. These marine organisms have shown different biological activities. The aim of this study was to investigate the effects of hexane and methanol extracts of Sargassum plagyophylum on depression. Methods Sargassum plagyophylum was collected from Persian Gulf. The plant was extracted by maceration with methanol-ethyl acetate solvent. The extract was evaporated and partitioned by hexane and methanol solvents. The two partitions were administered i.p. to male mice either a single dose or for 7 days. Depression was evaluated by the forced swimming test (FST) which higher immobility time indicates depressive-like behavior. Results The immobility time during FST decreased significantly by all the doses of the hexane partitions (notably 40 mg/kg; 10 s ± 2 vs. 114 s ± 12 control group). However, only the lowest dose (20 mg/kg) of the methanol partition reduced immobility time during FST (23 s ± 8, p<0.001). Following the long term administration both of the partitions reduced the immobility time in FST (hexane 27 s ± 11, methanol 70 s ± 14, p<0.05 vs. control 140 s ± 14). Conclusion The hexane partition showed antidepressant effects not only by long-term administration but also by the single dose during FST. The 7 days therapy with methanol partition also induced antidepressant behavior, but only the lowest single dose reduced immobility in FST. The methanol partitions possibly have certain substance that interfered with behavior in the FST. Therefore, S. plagyophylum should be considered for further antidepressant studies.

The effect of vitamin B6 on dexamethasone-induced depression in mice model of despair.

Objective: Glucocorticoid receptors (GRs) have an important role in mediating the effects of glucocorticoids (GCs) on brain plasticity and mood. GC drugs and elevated cortisol level can cause psychiatric disorders including depression. The B-vitamins have numerous benefits on general health as well as mood, and cognition. The aim was evaluating the effect of vitamin B6 following dexamethasone (DEX)-induced depression in mice, to see if it can be proposed as a remedy for psychiatric problems following GC therapy. Methods: Male mice were housed by six. The immobility time was measured, in the forced swimming test as an animal model of despair and sucrose preference was measured in order to test anhedonia (<65% was taken as a criterion for anhedonia). DEX was administered either single dose (15, 60, 250 mcg/kg) or 15 mcg/kg for 7 consecutive days, vitamin B6 (100 mg/kg) was administered for 7 days. Results: DEX dose dependently increased immobility time that denoted animal depression; as it was 177.5 seconds ± 3 following 60 mcg/kg and 188.3 seconds ± 5 following 250 mcg/kg administration (vs. control animals 164 seconds ± 6, P < 0.01). Premedication with vitamin B6 prevented DEX-induced depression and demonstrated antidepressant effect. It also reduced the immobility time following 7days DEX injection (192.5 seconds ± 6) to 100 seconds ± 5.5; sucrose preference escalated from 50%±3 to 87%±4. Conclusion: Vitamin B6 prevented DEX-induced depression possibly by altering the GR function. Thus Vitamin B6 could be promising in patients suffering from GC-induced psychiatric adverse effects and probably controlling stress and preventing its affective disorder out comes.

Evaluation of the effect of soybean diet on interferon-α-induced depression in male mice.

OBJECTIVE: Interferon-α (IFN) therapy can cause depressive symptom which may lead to drug discontinuation. By interfering with tryptophan pathway, the available level of tryptophan required for serotonin synthesis decreases which could be related to depression. The aim of this study was to evaluate whether soybean diet could improve IFN-induced depression. MATERIALS AND METHODS: Male mice weighing 28±3 g were used in the forced swimming test (FST) as an animal model of depression; also, locomotor activity was recorded. IFN 16×105 IU/kg was injected subcutaneously for 6 days. Animals were fed with regular diet or soybean diet at 3 concentrations throughout the experiment. Fluoxetine was the reference drug. To check whether the tryptophan content in the soy bean diet was effective, a group of animals was injected with a single dose of tryptophan on the test day. RESULTS: IFN-α increased the immobility time in the FST (192 sec ± 5.4), that denotes depression in mice. Soybean diets caused less immobility that was more profound with 50% soybean (26.4 sec ± 6). This diet overcame the depression caused by IFN in the FST (54 sec±18). This result was parallel with that of tryptophan injected to animals (38 sec±17). All the animals showed normal locomotor activity. CONCLUSION: For the first time, we showed that soybean diet could counteract with depression caused by IFN-α. Since tryptophan therapy had similar effects, possibly the tryptophan content of soybean had induced the serotonin synthesis. Thus, not only less harmful kynurenine was produced but also more serotonin was available in the brain to overcome depression. However, this interpretation needs further evaluations.

Effect of concomitant administration of three different antidepressants with vitamin B6 on depression and obsessive compulsive disorder in mice models.

Vitamin B6 is a cofactor of various enzymes influencing numerous neurotransmitters in the brain such as norepinephrin, and serotonin. Since these neurotransmitters influence mood, the aim the present work to evaluate the effect of vitamin B6 on depression and obsessive compulsive behavior when coadministred with clomipramine, fluoxetine, or venlafaxine. Male mice weighing 25-30 g were used. The immobility time and latency to immobility was measured in the forced swimming test as a model of despair and the number of marbles buried (MB) in an open field was used as the model of obsessive compulsive behavior in mice. Vitamin B6 (100 mg/kg, i.p.) was injected to animals for six days and on the last day antidepressants were also administered and the tests took place with 30 min intervals. Immobility was reduced in vitamin B6 + clomipramine (141 ± 15 s) or venlafaxine (116 ± 15 s) but it was not significant comparing with the drugs alone. No beneficial response was seen in co-administration of vitamin B6 with fluoxetine compared to fluoxetine alone. Fluoxetine also increased the latency to first immobility. Vitamin B6 + clomipramine or venlafaxine reduced the MB behaviour by 77 ± 12% and 83 ± 7% respectively, while using them alone was less effective. Fluoxetine was very effective in reducing MB behaviour (95 ± 3.4%) thus using vitamin B6 concomitantly was not useful. Therefore vitamin B6 as a harmless agent could be suggested in depression and particularly in obsessive compulsive disorder as an adjuvant for better drug response.

Learning and Memory Performance After Withdrawal of Agent Abuse: A Review.

CONTEXT: Agent abuse is a dire predicament worldwide. Learning and memory deficits stemming from the withdrawal of such agents is an increasingly burning issue for researchers. EVIDENCE ACQUISITION: The present review revisits the literature generated by far pertaining to the research on memory and cognition deficiencies after withdrawal of agent abuse and corresponding mechanisms. RESULTS: Deficiency on spatial memory, episodic memory and working memory are common after withdrawal of agent abuse. CONCLUSIONS: The present review suggests that memory dysfunction may result from withdrawal of agent abuse.

The effect of Cinnamomum zeylanicum bark water extract on memory performance in alloxan-induced diabetic mice.

Cinnamomum zeylanicum (cinnamon) has a wide range of beneficial effects including mild glucose lowering activity. The aim of the present study was to investigate whether cinnamon bark extract has the potential to improve memory performance and glucose profiles in diabetic mice. Memory was assessed by the novel object recognition task in male Balb/c mice. In this method, the difference between exploration time of a familiar object and a novel object was considered as an index of memory performance (recognition index, RI). The water extract was prepared by boiling cinnamon bark for 15 min. Alloxan induced diabetes in animals (serum glucose levels were 322 ± 7.5 mg/dL), and also impaired memory performance (RI= -3.3% ± 3.3) which differed significantly from control animals (RI = 32% ± 6.5). Although treatment with cinnamon only reduced fasting blood glucose level moderately but it improved memory performance remarkably (RI = 25.5% ± 5.6). Oxidative stress following administration of cinnamon extract was lower in diabetic mice. It was concluded that cinnamon water extract could be a useful alternative medicine in diabetic patients' daily regimen which not only reduces blood glucose levels but also improves memory performance and lipid peroxidation level.

The effects of Anethum graveolens essence on scopolamine-induced memory impairment in mice.

Since Anethum graveolens (Dill) has phytoestrogenic compounds and it is proven that estrogens exert beneficial effects on cognition; the aim of this study was to understand if this plant can improve memory performance. Male Balb/c mice weighing 25-30 g were used in this study and memory was assessed by the novel object recognition task. In this method, the difference in the exploration time between a familiar object and a novel object is taken as an index of memory performance (recognition index, RI). Scopolamine significantly reduced memory index (RI = -15.5% ± 3.0). Dill essence (100 mg/kg, ip) prevented the harmful effects of scopolamine on memory (RI = 40% ± 5.5), thus RI did not differ with control animals (RI = 50% ± 5.8). In addition, 17-ß estradiol also prevented memory impairment in animals (0.2 mg/kg, ip; RI = 35.8% ± 6.5). Nevertheless, the beneficial effects of dill essence were antagonized by prior injection of tamoxifen (1 mg/kg, ip; RI = -30% ± 7.8). Although phytoesrogens are not steroids, the beneficial effect of dill on memory, at least in part, may have been achieved by estrogenic receptors present in the brain. Thus dill essence could be promising in improving memory and cognition, mainly in postmenopausal women.

A Review on Ethnobotanical and Therapeutic Uses of Fenugreek (Trigonella foenum-graceum L).

Fenugreek with the scientific name of Trigonella foenum-graceum L and with leaves consisting of 3 small obovate to oblong leaflets is an annual herbaceous plant of the Fabaceae family. It is native to the eastern Mediterranean but is cultivated worldwide. This plant has medicinal alkaloids, steroid compounds, and sapogenins and many uses have been mentioned for this plant in traditional medicine. This plant has been used to ease childbirth, to aid digestion, and as a general tonic to improve metabolism. Trigonelline is considered as the most important metabolite of fenugreek, which is very effective in treating diabetes and decreasing blood cholesterol. Diaszhenin is another important compound in seeds of this plant, which is used in producing medicinal steroids like contraceptive pills. Many studies have been performed on the therapeutic effects and identification of chemical compounds of this plant. In this article, the most important biological effects and reported compounds about fenugreek seed are reviewed and its therapeutic applications are investigated.