Decreased Immobility Time Research Articles

Evaluation of the Behavioural, Antioxidative and Histomorphological Effects of Folic Acid-supplemented Diet in Dexamethasone-induced Depression in Mice.

The effect of folic acid in mitigating depression has remained pivotal in research. To determine the effects of folate supplementation on neurobehaviour oxidative stress and cerebral cortex histomorphology in the dexamethasone mouse model of depression. Male mice were assigned to six groups (A-F) of 10 mice each. Animals in groups A and D were fed a standard diet, while those in B and E were fed folic acid supplemented diet (25 mg/kg of feed), while C and F were fed folate supplemented diet at 50 mg/kg of feed for 8 weeks. At the beginning of the sixth 6th week, mice in groups A-C were administered distilled water, while animals in groups D-F were administered dexamethasone (DEX) at 4 mg/kg body weight by gavage. Open-field, forced swim, and tail-suspension tests were conducted at the end of the experimental period, following which animals were euthanised and blood was taken for the estimation of Malondialdehyde (MDA), reduced Glutathione, Glutathione Peroxidase, Catalase activity, and Superoxide Dismutase. Sections of the cerebral cortex were prepared for histological examination. Folic acid supplementation increased body weight, locomotor, rearing and self-grooming behaviours, and decreased immobility time in the tail suspension and forced swim tests. There was also a reduction of lipid peroxidation and an increase in the antioxidant status. Folic acid supplementation was also found to be protective against the development of dexamethasone-induced changes in body weight, open-field behaviours, behavioural despair, oxidative stress and cerebrocortical morphology. Folic-acid supplementation improves the behavioral, some antioxidant, and cerebral morphological parameters.

Induction of anxiolytic, antidepressant and analgesic effects by Shiff base of (E)-3-(1H-imidazol-4-yl)-2-((2-oxoindolin-3-ylidene)amino)propanoic acid derivatives in diabetic rats.

Diabetes mellitus is a metabolic disorder with several psychological problems such as anxiety, depression, and pain sense. This study aimed to evaluate the effect of Schiff base on the modulation of anxiety, depression, and pain behaviors in diabetic rats. Anxiety, depression, and pain behaviors were evaluated by elevated plus maze (EPM), forced swim test (FST), and hot-plate test, respectively. The results indicated that induction of diabetes decreased time spent in open arms (OAT) in the EPM whereas injection of insulin (1ml/kg), glibenclamide (5mg/kg), and Schiff base II (100mg/kg) increased OAT in the EPM. So, induction of diabetes in rats caused an anxiogenic effect that this effect reversed by drug treatment. Interestingly, co-treatment of insulin and glibenclamide along with an ineffective dose of Schiff base II potentiated anxiolytic behavior in diabetic rats. Furthermore, induction of diabetes increased immobility time in the FST but administration of insulin (1ml/kg), glibenclamide (5mg/kg), and Schiff base II (25, 50, and 100mg/kg) decreased immobility time in the FST which indicated depressant effect in diabetic rats without drug-treatment and antidepressant effect in diabetic rats with drug-treatment. Additionally, induction of diabetes decreased latency in the hot-plate test while injection of insulin (1ml/kg), glibenclamide (5mg/kg), Schiff base I (50mg/kg), and Schiff base II (25, 50, and 100mg/kg) enhanced latency in the hot-plate test which revealed hyperalgesic effect in diabetic rats without drug-treatment and analgesic effect in diabetic rats with drug-treatment. Consequently, induction of diabetes-induced anxiogenic, depressant, and hyperalgesia effects that administration of insulin, glibenclamide, Schiff bases I, and II reversed these effects.

A herbal syrup: Formulation and antidepressant effect in male rat

Introduction: Herbal medicines play a significant role in global health-care systems. In this investigation, a polyherbal syrup has been reformulated pursuant to Iranian traditional medicine and its antidepressant effect has been evaluated. Materials and Methods: The syrup was prepared by decocting a mixture containing: Lavandula angustifolia, Melissa officinalis, Echium amoenum, Cordia myxa, Glycyrrhiza glabra, Ziziphus jujuba, Foeniculum vulgare, Fumaria parviflora, Adiantum capillus-veneris, and Alhagi spp. along with glycerin and potassium sorbate. Physicochemical characteristics of the syrup were examined. An accelerated stability test was carried out for syrup as well. Moreover, antidepressant evaluations were performed by the forced swimming test using the drug as gavage (3.3 mL/kg/day) for three consecutive weeks. The serum levels of serotonin (5-HT), noradrenaline (NA), and brain-derived neurotropic factor (BDNF) were determined in rats as well. Finally histopathological examinations were done on liver, kidney and spleen. Results: The herbal syrup was brown in color with a special taste and flavor. Density, pH, viscosity, dry residue, and total phenolics content were 1.085g/ml, 5.56, 5.35 cP, 15.22%, and 194 mg/100 mL, respectively. The syrup was stable during accelerated stability tests, and no significant changes were observed. The polyherbal syrup exhibited significant antidepressant effects by decreasing immobility time through increasing in NA and 5-HT levels without affecting BDNF levels. Formulated syrup also did not have any toxic effects on the liver, kidney, and spleen. Conclusion: The syrup could be an appropriate candidate for pharmaceutical companies after complementary tests such as toxicity and clinical trials.

Chemical Profiling and Dose-Dependent Assessment of Fear Reducing and Memory-Enhancing Effects of Solanum virginianum in Rats.

The current study was planned to investigate the pharmacological basis of Solanum virginianum extract (SV.CR) pertaining to anxiolytic, antidepressant and memory-enhancing effects in rats. The SV.CR was analyzed in-vitro for phytoconstituents, antioxidant potential and anticholinesterase activity. The rats treated in a dose-dependent manner (25, 50 and 100 mg/kg of SV.CR) were subjected to behavioral tests for anxiety, depression and memory judgment followed by biochemical studies. A notable dose-dependent anxiolytic potential of SV.CR was observed in elevated plus maze and open field tests (P < 0.05). The decreased immobility time of the treated rats in the forced swim test (P < 0.01) unveiled the plant’s potential to reduce depression. Moreover, SV.CR treatment also reversed scopolamine-impaired cognition (P < 0.05) in various deployed memory and learning tasks. Biochemical studies of brain homogenates of SV.CR treated animals demonstrated decreased anticholinesterase activity and lipid peroxidation levels whereas increased levels of superoxide dismutase and glutathione peroxidase (P < 0.05 vs scopolamine group) were noted. The scientific validation of the study supported the use of Solanum virginianum in reducing anxiety, depression and amnesia in experimental models. Phytoconstituents in SV.CR such as oleanolic acid and caffeic acid might have played a significant neuroprotective role via modulation of oxidative stress and neurochemical aspects.

Medicinal Properties of Asparagus

Asparagus ia a vegetable and a medicinal or traditional herb. It has many health benefits because of its pharmacological properties and the active ingredients responsible for its effectiveness against various illnesses. A few medicinal Properties are discussed below:&#x0D; Anti-Inflammation Property of Asparagus&#x0D; Anti-inflammation can be defined as “It acts on body responses and reduce the inflammation, without directly counteracting the active agent such as glucocorticoids and aspirin”. One of these saponins has been of unique exuberance for relationship to amyotrophic horizontal sclerosis, otherwise called Lou Gehrig's Disease [1]. Even however amyotrophic parallel sclerosis is delegated a perpetual, neurodegenerative illness and isn't right now acknowledged as an immune system issue, over the top, undesirable irritation may assume an imperative part in the passing of certain nerve cells in amyotrophic sidelong sclerosis. In this mitigating setting, it is important that current research on the shatavarins in asparagus has uncovered another assemblage of saponins that impact aggravation through cytokine informing [2].&#x0D; Asparagus as the Best Antioxidant&#x0D; Analysts in Brazil has estimated the general reinforcement limit of asparagus. These specialists broke down twenty three ordinarily eaten vegetables in Brazil including asparagus. Their general outcomes demonstrated turmeric, watercress, lettuces, and broccoli to give the best general cancer prevention agent limit. Be that as it may, in a portion of the vegetables testing, asparagus turned out in the best ten among each of the twenty three vegetables for general cancer prevention agent limit. This finding isn't astonishing, given thenumerous customary and offbeat cell reinforcements show in asparagus. It merits recollecting here that asparagus positions as an astounding wellspring of both vitamin E and vitamin C two spotlight antioxidantas well as the mineral selenium, which assumes a key part in the capacity of glutathione peroxidase a standout amongst the most-examined cell reinforcement proteins in the body [3].The impact of methanolic concentrate of Asparagus pubescens was explored on compound, warm actuated agony and new egg whites incited aggravation. The concentrate measurement conditionally pent-up acidic corrosive incited wiggling, formalin-initiated torment licking and hot plate-actuated agony in mice. The concentrate essentially hindered the new egg whites prompted irritation in rats also. These hindrances were measurably critical [4].&#x0D; Antidepressant Activity&#x0D; The methanolic extract of asparagus demonstrated a decrease in immobility time in FST and TST in mice, which was comparable to imipramine and increase the levels of dopamine in vitro [5]. Futhermore, it was found to significantly brain monoamine oxidase levels as compared to control in a study focusing on finding the underlying mechanism of action, it was seen that methanolic extracts significantly inhibited cholinesterase and MAO activities [6]. In another study, antidepressant like activity was seen with methanolic root extract in FST and learned helplessness model [7].&#x0D; Anti Amnesic Activity&#x0D; Ethanolic root extract of asparagus was observed to produce a significant dose dependent enhancement of memory in the elevated plus maze model in mice [8]. The effect being significantly higher then the produced by piracetam [9]. Also there was an increase in the acetylcholinestrease levels in hippocampus areas associated with learning and memory [10]. In another study, methanolic exracts was found to reverse amnesia produced by scopolamine and sodium nitrate in the EPM and Morris water maze model in mice [11].&#x0D; Analgesic Action&#x0D; Aqueous and alcohalic root extracts of asparagus has been found to produce indicative analgesic action in heat conduction model. In another study, ethanolic extracts of asparagus was found to inhibit writing reflex in acetic acid induced writing model in mice [12].&#x0D; Antipyretic Action&#x0D; The ethanolic extracts of asparagus showed significant more antipyretic activity in albino Wistar rats than the aqueous extract in the yeast-derived pyrexia model, an effect comparable to normal antipyretic paracetamol [13]. Asparagus root extract which contains highest amount of flavonoids, polyphenols and vitamin-C exhibits the greatest antioxidant activity. Asparagus is likewise rich in flavonoid rutin&#x0D; REFERENCES

Acute antidepressant activity of ciprofloxacin and levofloxacin by using tail suspension test in swiss albino mice

Introduction: Depression is a psychological disorder of serious nature characterized by loss of interest in all most all the activities of life. In spite of many drugs available in the market, yet their is still search for newer drugs as the earlies drugs are known for its drawbacks like delayed onset of action and carries unacceptable adverse effects. Objectives: Our previous study with Ciprofloxacin and Levofloxacin have shown antidepressant activity by forced swim test in Swiss albino mice, hence we want to reconfirm the same in different models. Materials and Method: Swiss albino mice were divided randomly in to six groups of which each weighing 20-25 gm and the groups are as follows, Group I: 1% Gum acacia, 10ml/kg (Control), Group II: Imipramine (Standard), 10mg/kg, Group III and IV, Ciprofloxacin 25 & 50 mg/kg respectively, Group V & VI, Levofloxacin, 25 & 50 mg served as test group respectively. Each mouse was suspended by using a metal rod placed 50cm above the surface and its tail was pasted on to rod by an adhesive tape approximately 1cm away from the tip. Its mobility and immobility time was recorded discarding the initial 2minutes and considering the last 4 minutes of observation. Decrease in immobility time was considered to be having antidepressant effect. Results: Immobility duration based on mean± SD was 86.67 ± 2.61 sec for control, 52.50 ± 5.95 sec for Imipramine, 63.50 ± 19.00 sec and 67.17 ± 10.21 sec for Ciprofloxacin 25mg/kg and 50mg/kg respectively. Similarly, immobility duration for Levofloxacin was 68.67 ± 14.41 sec and 69.00 ± 18.85 sec respectively. Conclusion: Ciprofloxacin and Levofloxacin has not shown antidepressant activity by tail suspension test in Swiss albino mice. Keywords: Antidepressant, Ciprofloxacin, Levofloxacin, Tail suspension test

Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats

Chronic maternal ethanol exposure leads to poor intelligence, impaired cognition and array of neurological symptoms in offsprings and commonly referred as fetal alcohol spectrum disorder (FASD). Despite high prevalence and severity, the neurochemical basis of FASD remains largely unexplored. The present study evaluated the pharmacological effects of agmatine in cognitive deficits associated with FAS in rat’s offsprings prenatally exposed to alcohol. Pregnant rats received ethanol in liquid modified diet during the entire gestational period of 21 days. Offsprings were treated with agmatine (20–80 mg/Kg, i.p.) during early postnatal days (PND: 21–35) and subsequently evaluated for anxiety in elevated plus maze (EPM), depression in forced swim test (FST) and learning and memory in Morris’s water maze (MWM) during post adolescent phase. Hippocampal agmatine, BDNF, TNF-α and IL-6 levels were also analyzed in prenatally ethanol exposed pups. Offsprings prenatally exposed to ethanol demonstrated delayed righting reflex, reduced exploratory behavior along with anxiety, depression-like behavior and impaired memory. These behavioral abnormalities were correlated with a significant reduction in hippocampal agmatine and BDNF levels and elevation in TNF-α and IL-6 immunocontent. Chronic agmatine (40 and 80 mg/Kg, i.p.) administration for 15 days (PND: 21–35), improved entries and time spent in open arm of EPM, decreased immobility time in FST. It also reduced latency to reach the platform location; increased the number of entries, time spent in platform quadrant and also number of crossing over platform quadrant when subjected to MWM test in prenatally ethanol exposed offsprings. This study provides functional evidences for the therapeutic potential of agmatine in cognitive impairment and other neurological complications associated with FASD.

Antidepressant-Like Properties of Fish Oil on Postpartum Depression-Like Rats Model: Involvement of Serotonergic System.

Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, the current study aimed at investigating the effects of FO on a PPD-like rat model. Female rats were induced with PPD-like symptoms and then randomly divided into six groups (n = 6) for two experimental protocols. Protocol 1 consisted of PPD-like rats (2 mL distilled water), PPD-like + FO (9 g/kg/d) and PPD-like + Fluoxetine (FLX) (15 mg/kg/d) groups of rats, whereas Protocol 2 consisted of PPD-like rats (2 mL distilled water) + PCPA (p-chlorophenylalanine) 150 mg/kg, PPD-like + FO (9 g/kg/d) + PCPA 150 mg/kg and PPD-like + FLX (15 mg/d) + PCPA 150 mg/kg groups of rats, respectively. All treatments were administered orally for 10 days postpartum, except PCPA, which was given intraperitoneally. Prior to euthanasia, the antidepressant-like effect of the FO was evaluated using the forced swimming test (FST) and open field test (OFT) on day 10 postpartum. Biochemical analysis of serotonin, serotonin metabolite and serotonin turnover from their prefrontal cortex and hippocampus were also measured. The results showed that FO decreased immobility time and increased swimming time significantly, but not climbing time in FST. Further, it also decreased serotonin metabolite and turnover significantly in the hippocampus of the PPD-like rats. In contrast, administration with PCPA reversed all the outcomes. The antidepressant-like effects of FO were found to be similar with that of FLX. Thus, it can be concluded that FO exerts its antidepressant-like effects in PPD-like rats through modulation of serotonergic system.

Concurrent environmental enrichment and chronic restraint stress: Effects on innate anxiety and depressive-like behavior in male adolescent mice.

Adolescence is a period that exhibits both vulnerability and adaptation to environmental stimulus. This study explored the co-existence effect of environmental enrichment (EE) and restraint stress (RS) on innate anxiety and depressive-like behavior in adolescent mice. Male ICR mice were treated with daily EE and RS (4h/d or 8h/d) for 2 or 4weeks from early adolescence (postnatal day 30) and emotional behaviors were evaluated 24h after the end of treatment. 4 weeks of 8h RS treatment decreased immobility time in forced swimming test, demonstrating an antidepressant-like effect. For 2weeks of treatment, 8h RS significantly reduced the time spent in the lighted compartment of the light-dark box, indicating an increased anxiety level. These results show that under the present experimental design, RS treatment with different duration could have different effect on mice emotion-related behavior, but there was no interaction between EE and RS.

Effects of adipokinetic hormone/red pigment-concentrating hormone family of peptides in olfactory bulbectomy model and posttraumatic stress disorder model of rats

One of the major neuropeptide groups in insects is adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. AKH had improving effects on depression and anxiety in animal models and it may be a new treatment choice in these disorders. Aim of this study was to investigate effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH) and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on animal behavior in olfactory bulbectomy (OBX) model and in posttraumatic stress disorder (PTSD) model of Wistar-albino rats. Lia-AKH and Pht-HrTH significantly increased time spent in escape platform’s quadrant compared to sham control while Lia-AKH significantly increased time spent in escape platform’s quadrant compared to OBX controls in probe trial of Morris water maze (MWM). Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased immobility time compared to OBX controls in forced swimming test (FST). Pht-HrTH significantly increased %open arm time compared to OBX controls in elevated plus maze (EPM) test. Ani-AKH significantly increased %open arm entry compared to sham control while Ani-AKH and Pht-HrTH significantly increased %open arm entry compared to OBX controls in EPM. In PTSD study Ani-AKH and Lia-AKH significantly decreased immobility time compared to traumatized controls in FST. In acoustic startle reflex test, Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased average startle amplitude compared to non-traumatized controls in PTSD study. Metabolomic studies showed that AKH may affect glutamatergic and dopaminergic system and neurochemistry. In conclusion, AKH peptides had wide ranging effects on behavior and improved performance in OBX and PTSD models in rats.

The deleterious effect of stress-induced depression on rat liver: Protective role of resveratrol and dimethyl fumarate via inhibiting the MAPK/ERK/JNK pathway.

This study aimed to uncover the protective potentiality of resveratrol and dimethyl fumarate (DMF) in the liver of a chronic unpredictable mild stress (CUMS)-induced depression animal model. Resveratrol and DMF significantly alleviated CUMS-induced behavioral abnormalities in stressed rats through improving sucrose preference in sucrose preference test and decreasing immobility time in a forced swimming test. They also mitigated serum corticosterone levels and elevated serum serotonin levels, which were formerly disturbed in CUMS rats. The hepatoprotective effect is evidenced by improvement in hepatic histopathological examinations, as well asnormalized serum alanine aminotransferase and aspartate aminotransferase activities. Molecular signaling of resveratrol and DMF was estimated by diminishing hepatic expression of phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK). Consequently, they improved the hepatic antioxidant and anti-inflammatory activities as elaborated by the normalization of total antioxidant capacity, glutathione, malondialdehyde, nuclear factor-κB, tumor necrosis factor-α, and myeloperoxidase levels. In addition, they inhibited hepatocyte apoptosis as evidenced by the increased expression of B-cell lymphoma 2, the decreased expression of Bax, as well asthe suppressed activity of caspase-3. In conclusion, resveratrol and DMF purveyed a significant anti-depressant effect, which may be mediated, at least in part, via inhibiting the MAPK/ERK/JNK pathway in the CUMS rat model.

Effects of Hesperidin During Pregnancy on Antidepressant-like behaviour in Postpartum Mice

BACKGROUND:Post-partum depression is the most prevalent form of mental illness and herbal therapies are potential alternatives and adjuncts for its treatment. Hesperidin is the major flavonoid isolated from cit- rus fruits which has neuroprotective, antioxidant and antidepressant activity. OBJECTIVES: We studied the effect of exposure to Hesperidin during pregnancy on postpartum antide- pressant-like effects in mice. METHODS: Twelve male and 40 female mice (28-30 gr) were randomly selected and after determina- tion of the pregnancy using vaginal plaque, allocated into 4 experimental groups. Group 1 was kept as control and groups 2-4 were i.p. injected with 0.1, 0.5 and 1 mg/kg of hesperidin on days of 5, 8, 11, 14 and 17 of pregnancy. The control group received i.p. injection of the saline on the same days. Following postpartum, forced swimming test (FST), tail suspension test (TST) and open field tests were used to eval- uate depressive-like antidepressant activity of hesperidin. At the end of the study, serum Malondialde- hyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and total antioxidant capacity (TAC) were determined. RESULTS: According to the results, administration of the different levels of the hesperidin (0.5 and 1 mg/ kg) at GD 5, 8, 11, 14 and 17 significantly decreased immobility time (S) in TST and FST on postpartum mice compared to control group (p ≤0.05). Pre-partum administration of hesperidin (0.1, 0.5 and 1 mg/kg) had no significant effect on OFT of control group (p >0.05). Administration of the hesperidin (0.5 and 1 mg/ kg) during the GD significantly decreased MDA levels on postpartum compared to control group (p ≤0.05). Also, pre-partum administration of the hesperidin (0.1, 0.5 and 1 mg/kg) significantly increased SOD and GPx levels on postpartum mice compared to control group (p ≤0.05). CONCLUSIONS: These results suggested pre-partum administration of hesperidin has antidepressant and antioxidant effect in postpartum mice.

Protective effects of Biarum carduchrum ethyl acetate extract on seizure severity, depression, memory, and learning in pentylenetetrazole-induced kindling rats Running title: Biarum carduchrum effects on seizure, oxidative stress, and cognitive impairment

Background: Based on traditional beliefs, Biarum carduchrum (family Araceae) can strengthen the nervous system and prevent from sleep disorder and agitation. Objectives: This study was performed to investigate the protective effects of the ethyl acetate extract of Biarum carduchrum leaves against pentylenetetrazol (PTZ)-induced seizure in rats. Methods: The present experimental research was conducted on 50 male Wistar rats in Iran during 2019. The animals were examined in five groups of control, PTZ, intervention (PTZ with 100 and 200 mg/kg ethyl acetate extract for 10 days), diazepam (PTZ, 200 mg/kg extract, and diazepam). The research groups were compared in terms of behaviors. Furthermore, total phenol and flavonoid levels in the extract were determined using high-performance liquid chromatography. Results: According to the results, the intervention and diazepam groups had a significantly lower number of the whole body, tonic, head, and upper organ seizures (P&lt;0.05), and jumps (P&lt;0.05), compared to the PTZ group. Both doses of the extract also significantly decreased immobility time in tail suspension and secondary latency time and significantly enhanced spatial memory in Morris water maze test (P&lt;0.05). This treatment also significantly reduced the levels of nitric oxide and malondialdehyde in the brain and serum (P&lt;0.05) and showed antioxidant activity (IC50=200 μg/ml). The extract contained 42.63±0.7494 and 85.16±6.499 µg/mg phenol and flavonoid, respectively. The HPLC analysis also revealed the presence of quercetin (30 μg/g) in the extract. Conclusions: Based on the results, Biarum carduchrum extract can be used for depression control and improvement of learning and memory impairments in seizure patients after complementary testing.

The Antidepressant-Like Effects of Hesperidin in Streptozotocin-Induced Diabetic Rats by Activating Nrf2/ARE/Glyoxalase 1 Pathway.

The co-occurrence of diabetes and depression is a challenging and underrecognized clinical problem. Alpha-carbonyl aldehydes and their detoxifying enzyme glyoxalase 1 (Glo-1) play vital roles in the pathogenesis of diabetic complications, including depression. Hesperidin, a naturally occurring flavanone glycoside, possesses numerous pharmacological properties, but neuroprotection by hesperidin in depression-like behaviors in diabetes was not observed. This study aimed to investigate the mechanisms and signaling pathways by which hesperidin regulates depression-like behaviors in diabetic rats and to identify potential targets of hesperidin. Rats with streptozotocin-induced diabetes were treated orally with hesperidin (50 and 150 mg/kg) or the nuclear factor erythroid 2-related factor 2 (Nrf2) inducer tert-butylhydroquinone (TBHQ, 25 mg/kg) for 10 weeks. After behavioral test, the brains were collected to evaluate the effects of hesperidin on Glo-1, Nrf2, protein glycation, and oxidative stress. Hesperidin showed antidepressant and anxiolytic effects in diabetic rats, as evidenced by the decreased immobility time in the forced swimming test, increased time spent in the center area of the open field test, and increased percentage of open-arm entries and time spent in the open arms in the elevated plus maze, as well as by the enhancement of Glo-1 and the inhibition of the AGEs/RAGE axis and oxidative stress in the brain. In addition, hesperidin caused significant increases in the Nrf2 levels and upregulated γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling. In vitro, the effects of hesperidin on N2a cell injury caused by high glucose (HG) was assessed by MTT and LDH, and the effects on Nrf2 signaling were also assessed. We found that the Nrf2 inhibitor ML385 reversed the protective effects of hesperidin on the cell injury induced by HG. Hesperidin prevented the HG-induced reduction in the Nrf2 and Glo-1 levels, and ML385 reversed the effects of hesperidin on the expression of the proteins mentioned above, indicating that Nrf2 signaling is involved in the hesperidin-induced neuroprotective effects. Our findings indicate that the effects of hesperidin on ameliorating the depression- and anxiety-like behaviors of diabetic rats, which are mediated by the enhancement of Glo-1, may be due to the activation of the Nrf2/ARE pathway.

Antidepressant-like effects of solidagenone on mice with bacterial lipopolysaccharide (LPS)-induced depression

BackgroundConsidering the pharmacological potential of solidagenone from Solidago chilensis, the present investigation was carried out to evaluate its antidepressant-like effect in mice with bacterial lipopolysaccharide (LPS)-induced depressive like behavior and its mode of action through the measurement of neuroinflammatory and oxidative markers. Materials and methodsIn the prophylactic test, the mice were pretreated with solidagenone (1, 10 or 100 mg/kg, p.o) and after one hour received LPS. In therapeutic test, the mice received LPS and after 5 h were treated with solidagenone (1, 10 or 100 mg/kg, p.o). In both experimental approaches, the animals were submitted to OFT and to the TST after 6 and 24 h of the LPS administration, respectively. One hour after the TST the animals were euthanized, the blood was collected, the cortex was removed and biochemical analyzes were performed for measurement of the inflammatory and oxidative stress markers. ResultsThe LPS induced sickness- and depressive-like behaviors and increased the cortical activity of myeloperoxidase (MPO), as well as the IL-6 and TNF amount. Interestingly, the pretreatment with solidagenone at 100 mg/kg avoided the behavioral alterations in OFT. In the mice post treated with solidagenone, all tested doses of resulted in an antidepressant-like effect evidenced by the decrease in immobility time in the TST. This effect was accompanied by a decrease in the MPO activity and in the IL-6 and TNF levels in the cortex in parallel to the increase in catalase activity. ConclusionsThe solidagenone has a promissor antidepressant-like potential, which can result of its beneficial action in the neuroinflammation process and due its antioxidant capability at the central nervous system.

Antidepressant and anti-amnesic effects of the aqueous lyophilisate of the leaves of Leptadenia arborea on an animal model of cognitive deficit associated depression

Leptadenia arborea (Asclepiadaceae) is a plant used in traditional medicine to treat syphilis, migraine, and mental illnesses. The aim of our study was to investigate possible antidepressant and anti-amnesic effects of the aqueous lyophilisate of the leaves of Leptadenia arborea in an animal model of cognitive deficit associated depression. Swiss albino adult mice of both sexes were used for this study. A 14-day combined stress model was used to induce depression with early cognitive deficits. The forced swimming test, the open field test and plasma corticosterone level were used to assess antidepressant-like effect. The novel object recognition task (NORT), the Morris Water Maze (MWM) and neurochemical analysis of hippocampal acetylcholinesterase activity was also carried out to assess memory integrity. The aqueous lyophelisate of L. arborea increased swimming time and decreased immobility time in the forced swimming test. In the open field test they was no difference in the number of lines crossed between groups, and the lyophilisate-treated mice spent more time in the centre compared to the control. The lyophilisate decreased the plasma level of corticosterone compared to the control. The lyophilisate decreased the latency to reach the hidden platform and increased the time spent in the target quadrant in the MWM. The lyophilisate also increased the time of exploration of the novel object in the NORT and decreased the acetylcholinesterase activity in the hippocampus. L. arborea effects were decreased when it was co-administered with pCPA. Results suggest that the aqueous lyophilisate of the leaves of L. arborea possess antidepressant-like and anti-amnesic effects.

Rostromedial tegmental nucleus-substantia nigra pars compacta circuit mediates aversive and despair behavior in mice

GABAergic neurons in the rostromedial tegmental nucleus (RMTg) receive major input from the lateral habenula (LHb), which conveys negative reward and motivation related information, and project intensively to midbrain dopamine neurons, including those in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). The RMTg-VTA circuit has been shown to be linked to the affective behavior, but the role of the RMTg-SNc circuit in aversion and depression has not been well understood. This study demonstrated that exciting or inhibiting VgatRMTg-SNc neurons was sufficient to increase or decrease immobility time in the forced swim test (FST), respectively. Furthermore, exciting the VgatRMTg-SNc pathway caused aversive behavior. Ninety percent of the SNc putative dopamine neurons were inhibited in extracellular recordings. Furthermore, inhibiting the VgatRMTg-SNc pathway reversed behavioral despair in chronic restraint stress (CRS) depression model mice. Manipulations of the pathway did not affect the hedonic value of the reward in the sucrose-preference test (SPT) or general motor function. In conclusion, these results indicate that the VgatRMTg-SNc pathway regulates aversive and despair behavior, which suggests that the RMTg may mediate the role of LHb in negative behaviors through regulating the activity of SNc neurons.

The duration of the antidepressant-like effects of a single infusion of brain-derived neurotrophic factor into the medial prefrontal cortex in mice

Rapid release of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) plays a critical role in the rapid and sustained antidepressant actions of ketamine, an N-methyl-d-aspartate receptor antagonist. Although our recent studies demonstrated that a single infusion of recombinant BDNF (100 ng/side) into the mPFC produced rapid antidepressant behavioral responses, the duration of the antidepressant-like effects of the single dose is unclear. Herein, we examined the duration of the antidepressant-like effects of intra-mPFC infusion of BDNF using male C57BL/6 J mice in two different behavioral paradigms namely, despair (forced swim test, FST) and motivation/reward (female urine sniffing test, FUST). Intra-mPFC BDNF infusion significantly decreased immobility time in the FST on days 1 and 7, but not 14 after the infusion. Similarly, BDNF significantly increased the time spent sniffing female urine in the FUST on days 3 and 8, but not 15 after the infusion. Intra-mPFC infusion of BDNF did not affect locomotor activity 2 days after the infusion. These results indicate that the antidepressant-like effects of a single intra-mPFC infusion of BDNF last for approximately one week and that this duration is similar to that of the antidepressant actions of ketamine.

Activation of BDNF-mediated PKA signaling in the ventral hippocampus by Capsosiphon fulvescens glycoproteins alleviates depressive-like behavior in aged rats

• Cf-hGP downregulated immobility time of aged rats in forced swimming test. • mBDNF expression in the ventral hippocampus was upregulated by Cf-hGP. • BDNF-mediated PKA signaling by Cf-hGP increased AMPAR GluR1 phosphorylation. • Activation of PKA signaling by Cf-hGP also decreased JNK-mediated ER stress. • AMPAR blockade or PKA inhibition abolished Cf-hGP-induced decrease in immobility time. Aging is associated with an increased risk of emotional disorders such as depression. In this study, effects of Capsosiphon fulvescens hydrophilic glycoproteins (Cf-hGP) on depressive-like behavior in aged rats were investigated. Oral administration of Cf-hGP (15 mg/kg/day; 4 weeks) attenuated immobility time of aged rats in forced swimming test by increasing expression of mature brain-derived neurotrophic factor (BDNF) in the ventral hippocampus. Cf-hGP-induced BDNF-mediated activation of extracellular signal-regulated kinase (ERK)1/2 increased cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) phosphorylation, which upregulated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluA1 phosphorylation at serine 845. The activation of BDNF-mediated PKA signaling by Cf-hGP also attenuated endoplasmic reticulum (ER) stress in the ventral hippocampus. AMPAR blockade or PKA inhibition abolished the Cf-hGP-induced decrease in immobility time. These findings suggest that BDNF-mediated cAMP/PKA signaling in the ventral hippocampus contributes to antidepressant effects of Cf-hGP by regulating AMPAR GluA1 phosphorylation and ER stress.

Optimizing the Synergistic Effects of Cannabidiol and Δ9-Tetrahydrocannabinol for the Treatment of Neuropathic Pain in Mouse Behavioural Models

Introduction: The analgesic properties of CBD and THC in cannabis can potentially be leveraged for the treatment of neuropathic pain but have not been well investigated. Some commercial analgesics, such as opioids, have unfavourable side effects including addiction, which does not exist in cannabis. Combinations of CBD and THC may not only elicit stronger analgesic effects than single-compound drugs, but also curb the psychotropic effects commonly associated with THC. We present a novel protocol to find the ideal substance ratio in a CBD-THC mixture, which elicits maximum antinociception with the least psychotropic effect. Methods: BALB/c mice will be assigned to 12 different treatment groups, representing 9 different ratios of CBD-THC mixtures, 2 positive controls (URB937 and sertraline hydrochloride), and 1 vehicle. Each mouse will be administered a compound via intraperitoneal injection and then subjected to behavioural testing. Chronic constriction injury and the Hargreaves’ Test (HT) will be used to test nociceptive behaviour while the Tail Suspension Test (TST) will be used to test depression-like behaviour. Expected Results: The ideal CBD-THC mixture will produce maximum withdrawal latency in the HT and maximum immobility time in the TST. Because the analgesic properties of combined CBD and THC still remain unclear in current literature, it is difficult to predict how withdrawal latency in the HT will change with varying CBD:THC ratios. Based on the psychotropic effects of THC, we expect increased THC concentrations to decrease immobility time in the TST. Conclusion: By determining the optimal ratio of CBD:THC for maximal pain suppression and minimal psychotropic effects, our protocol may provide justification for an alternative non-addictive therapeutic for treating neuropathic pain. In order to increase the generalizability and translatability of the results in a clinical setting, future studies could benefit from changes in dosing strategies, routes of administration, supplemental observation methods, and experimental timeframes.