Decreased Immobility Time Research Articles

The antidepressant-like effects of Origanum majorana essential oil on mice through monoaminergic modulation using the forced swimming test

Origanum majorana (L.) is an herb used in the treatment of diseases related to the nervous system in traditional medicine (e.g. as an anticonvulsant and sedative). The present study was conducted to investigate the antidepressant-like effects of Origanum majorana essential oil (OMEO) on mice in the forced swimming test (FST). The animals were intraperitoneally (i.p.) injected with OMEO (10–80 mg/kg) 1 h before the FST. To assess the involvement of the monoaminergic system in the antidepressant activity of OMEO, different pharmacological antagonists were administered 15 min before OMEO administration (80 mg/kg). The administration of OMEO (40 and 80 mg/kg, i.p.) decreased immobility time and increased swimming and climbing times significantly. OMEO did not cause any changes in spontaneous locomotor function in the open-field test (OFT). The pre-treatment of the animals with SCH23390, sulpiride, haloperidol, WAY100135, p-chlorophenylalanine (pCPA), ketanserin, prazosin, yohimbine, reserpine, but not propranolol, inhibited the anti-immobility effect of OMEO in the FST. A combination of sub-effective doses of fluoxetine (5 mg/kg, i.p.) or imipramine (5 mg/kg, i.p.) with OMEO (10 mg/kg, i.p.) increased the antidepressant-like effects. OMEO showed antidepressant-like effects through involvement with the dopaminergic (D1 and D2), serotonergic (5HT1A, 5-HT2A receptors) and noradrenergic (α1 and α2 adrenoceptors) systems.

Investigation of Antistress Activity of Operculina Terpethum Roots using Various Experimental Models

The root part of Operculina terpethum has been widely used in Ayurveda to treat variety of common and stress related disorders. The antistress effect of a seven-days treatment (100 and 200 mg / kg, p.o.) of the 80% ethanolic extract of Operculina terpethum root (OTRE) was evaluated by using the swimming endurance test, anoxic tolerance test, and biochemical changes in the cold-restraint stress test. The immunomodulatory activity was also evaluated for the same doses, and treatment of OTRE using the hem agglutination test. Diazepam 1 mg/kg was used as reference standard for the comparison. Both the doses of OTRE showed anti stress activity in all the tested models. 7 days pretreatment of OTRE (100 and 200 mg / kg, p.o.) treated animals showed a decrease in immobility time and an increase in anoxic tolerance time in swimming endurance and the anoxic tolerance tests, respectively. Pretreatment with OTRE significantly ameliorated the cold restraint stress induced variation in biochemical level such as increase in plasma cholesterol, triglyceride, glucose, total protein, and cortisol. Further, OTRE treatment significantly inhibited cold restraint stress induced alteration in brain noradrenaline, dopamine and serotonin levels. In mice immunized with sheep red blood cells, the treatment groups subjected to restraint stress prevented the humoral immune response to the antigen. The immune stimulating activity of the OTRE was indicated by an increase in the antibody titer in mice pre-immunized with sheep red blood cells and subjected to restraint stress. The findings of the present investigations indicate that the OTRE has significant anti stress activity, which may be due to the immune stimulating property and increased resistance, nonspecifically, against all experimental stress conditions.

Use of magnoflorine-phospholipid complex to permeate blood-brain barrier and treat depression in the CUMS animal model

To improve the liposolubility and blood-brain barrier permeability of magnoflorine, a new formulation of magnoflorine-phospholipid complex was prepared, characterized, and pharmacologically evaluated in the chronic unpredictable mild stress animal model. In this paper, the magnoflorine-phospholipid complex was synthesized and its characterization was determined. The antidepressant-like and antioxidant activity of magnoflorine-phospholipid complex was investigated by behavioral tests and western blotting analysis. As a result, the magnoflorine-phospholipid complex displayed high encapsulation efficiency and significantly improved the oil-water participate coefficient. In vivo blood-brain distribution study, the magnoflorine-phospholipid complex extended the duration of magnoflorine in blood and help magnoflorine to permeate the blood-brain barrier into brain. In behavioral tests, the magnoflorine-phospholipid complex significantly decreased immobility time compared to model control group in both FST and TST. Furthermore, the magnoflorine-phospholipid complex increased the expression of antioxidative stress-related proteins by the western blotting analysis. These findings strongly suggest that the phospholipid complex could significantly improve liposolubility, drug properties of magnoflorine and help magnoflorine permeate blood-brain barrier and exert the antidepressant effect.

What is the role of subcutaneous single injections on the behavior of adult male rats exposed to drugs?

Psychostimulants, as well as cannabinoids, have been shown to significantly affect a great variety of behaviors in both humans and laboratory animals. Our previous studies have repeatedly demonstrated that the application of the vehicle for psychostimulants, i.e. saline, to control groups, generated different behavioral test results compared to absolute naive controls (i.e. without any injection). Therefore, our present study has set three goals: (1) to evaluate the effect of three different psychostimulant drugs, (2) to evaluate the effect of three doses of delta 9-tetrahydrocannabinol (THC), and (3) to evaluate the effect of saline and ethanol injections vs sham injections and no injection on spontaneous behavior of adult male rats. The LABORAS test (Metris B.V., Netherlands) was used to examine spontaneous locomotor activity and exploratory behavior in an unknown environment over 1 h. In Experiment 1, psychostimulant drugs were tested: single subcutaneous (s.c.) injections of amphetamine (5 mg/kg), cocaine (5 mg/kg), and 3,4-methylenedioxymethamphetamine (MDMA) (5 mg/kg) were applied prior to testing. Control animals received the same volume (1 ml/kg) of s.c. saline. In Experiment 2, the effect of three doses of THC (1, 2, and 5 mg/kg, s.c.) were examined. An s.c. injection of vehicle (ethanol) was used as a control. In Experiment 3, injections of saline and ethanol were compared to the group receiving a sham s.c. injection and to a group of absolute "naive" controls. Our results demonstrated that (1) all psychostimulants increased locomotion time, distance traveled, and speed while decreasing immobility time of adult male rats relative to saline controls. The most prominent effect was associated with MDMA; (2) The effect of THC was dose-dependent and was most apparent within the first 10 min of the LABORAS test. (3) With regard to the effect of injection: absolute controls (without injection) compared to animals injected with ethanol, saline, or sham-injected displayed reduced immobility time, traveled longer distances, and had increased speed. In conclusion, our data showed drug dependent behavioral changes in adult male rats after application of psychostimulants and cannabinoids. Our findings also suggest that not only drugs but the actual single injection per se also affects the behavior of laboratory animals in an unknown environment. This effect seems to be associated with the acute stress associated with the injection.

Blockade of nicotinic acetylcholine receptor enhances the responsiveness to bupropion in the mouse forced swim test

The objective of the present study is to investigate the role of α4, α5, α6 or β2 nAChR subunits in the antidepressant-like effect of bupropion. Adult male mice were treated with subcutaneous acute doses of bupropion (3 and 10 mg/kg) 30 min before the forced swim test (FST) in α4, α5, α6, or β2 nAChR subunit knockout (KO) and wild-type (WT) mice. In addition, the effects of β2* antagonist dihydro-β-erythroidine (DHβE, 3 mg/kg) on antidepressant-like effects of bupropion in C57BL/6 J mice were assessed. Our results showed that baseline immobility and climbing time did not differ between KO and corresponding WT mice except for β2 KO. Bupropion significantly decreased immobility time and increased climbing time in the α4, α6 and β2 nAChR KO mice in comparison to WT littermates, indicating that lack of these nAChR subunits enhanced antidepressant effects of bupropion. On the contrary, the α5 nAChR subunit deletion did not alter the FST behavior in the bupropion-treated mice. Not only in the transgenic mice, bupropion also showed antidepressant-like effects in the WT mice. In addition, DHβE pretreatment before bupropion administration resulted in decreased immobility time and increased climbing time. Taken together, the present study provides evidence on the involvement of α4*, α6*, and β2* (* indicates possible presence of other subunits) nAChRs in the antidepressant-like effects of bupropion in the FST.

Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice

Flavonoids are naturally occurring bioactive phytochemical metabolites widely known to prevent and suppress several human diseases, and are important sources of therapeutic compounds from plants. Evidence derived from previous studies suggests that naringin, a neuroactive flavonoid possess functional beneficial neurobehavioral effects including anxiolytic, antidepressant and memory enhancing properties. However, literature search revealed that no studies have been carried out to evaluate the possible biochemical mechanisms involved in the neurobehavioral property of naringin alone following repeated treatment. Hence, this study was designed to evaluate the possible neuro-biochemical mechanisms involved in the neurobehavioral property of naringin following repeated administration in mice. The effects of naringin (2.5, 5 and 10 mg/kg), diazepam (2 mg/kg), imipramine (15 mg/kg) and donepezil (1 mg/kg) or vehicle on neurobehavioral and biochemical effects were evaluated in mice following repeated intraperitoneal injection for 7 consecutive days. Neurobehavioral activities consisting of open-field (locomotor), elevated-plus maze (anxiolytic), forced swim and social interaction (antidepressant and social preference), and Y-maze (memory enhancing) tests were assessed. Thereafter, brains levels of biomarkers of oxidative, nitrosative and cholinergic parameters were determined. Repeated treatment with naringin produced increased locomotor activity, and demonstrated antidepressant-like effects evidenced by decreased immobility time in forced swim test and increased % social preference in the social interaction test relative to controls. Also, naringin induced anxiolytic-like effect and increased cognitive performance in mice. Mechanistically, naringin significantly increased the activities of superoxide dismutase and catalase, and glutathione concentration relative to vehicle-controls. However, naringin significantly decreased malondialdehyde and nitrite contents, and reduced brain acetylcholinesterase activity in mice brains in a significant manner relative to controls. Taken together, these findings suggest that treatment with naringin might be useful to produce functional behavioral effects via mechanisms related to enhancement of cholinergic transmission, antioxidant defense systems, inhibition of lipid peroxidation and nitrosative processes.

Long-lasting antidepressant-like activity of the GPR39 zinc receptor agonist TC-G 1008

BackgroundThe discovery of the zinc-sensing receptor, has provided new possibilities for explaining the neurobiology of zinc. Recent studies indicate that the GPR39 zinc receptor may play an important role in the pathogenesis of depression as well as in the antidepressant mechanism of action. MethodsIn this study we evaluated the time-course of the antidepressant response of the GPR39 agonist (TC-G 1008), imipramine, ZnCl2 and MK-801 in the forced swim test in mice 30 min, 3 h, 6 h and 24 h after acute drug administration as well as after 14-day treatment. Zinc level was measured in serum of mice. BDNF protein level was evaluated in hippocampus following both acute and chronic TC-G 1008 treatment. ResultsA single administration of the GPR39 agonist caused an antidepressant-like effect lasting up to 24 h following the injection, which is longer than the effect of imipramine, ZnCl2 and MK-801. Chronic treatment with these compounds caused a decrease in immobility time in the FST. Serum zinc concentrations showed an increased level following chronic ZnCl2 administration, but not following administration of TC-G 1008, imipramine or MK-801. We also observed some tendencies for increased BDNF following acute TC-G 1008 treatment. LimitationsTC-G 1008 is new drug designed to study GPR39 therefore additional pharmacodynamic and pharmacokinetic properties in preclinical studies are required. ConclusionThis study shows for the first time the long-lasting antidepressant effect of the GPR39 agonist in comparison with imipramine, ZnCl2 and MK-801. Our findings suggest that GPR39 should be considered as a target in efforts to develop new antidepressant drugs.

Near-infrared photobiomodulation combined with coenzyme Q10 for depression in a mouse model of restraint stress: reduction in oxidative stress, neuroinflammation, and apoptosis

This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q10 (CoQ10) on depressive-like behavior, cerebral oxidative stress, inflammation, and apoptosis markers in mice. To induce a depressive-like model, mice were subjected to sub-chronic restraint stress for 5 consecutive days. NIR PBM (810 nm laser, 33.3 J/cm2) and/or CoQ10 (500 mg/kg/day, gavage) were administered for five days concomitantly with immobilization. Behavior was evaluated by the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Mitochondrial membrane potential as well as oxidative stress, neuroinflammatory, and markers of apoptosis were evaluated in the prefrontal cortex (PFC) and hippocampus (HIP). The serum levels of pro-inflammatory cytokines, cortisol, and corticosterone were also measured. PBM or CoQ10, or the combination, ameliorated depressive-like behaviors induced by restraint stress as indicated by decreased immobility time in both the FST and TST. PBM and/or CoQ10 treatments decreased lipid peroxidation and enhanced total antioxidant capacity (TAC), GSH levels, GPx and SOD activities in both brain areas. The neuroinflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels in PBM and/or CoQ10 groups. Intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and -9, were also significantly down-regulated by both treatments. Furthermore, both treatments decreased the elevated serum levels of cortisol, corticosterone, TNF-α, and IL-6 induced by restraint stress. Transcranial NIR PBM and CoQ10 therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.

Venlafaxine Mitigates Depressive-Like Behavior in Ovariectomized Rats by Activating the EPO/EPOR/JAK2 Signaling Pathway and Increasing the Serum Estradiol Level.

Reduced estradiol levels are associated with depression in women during the transition to and after menopause. A considerable number of studies focusing on the theme of treating depression through the activation of erythropoietin (EPO)-induced signaling pathways have been published. Venlafaxine is an approved antidepressant drug that inhibits both serotonin and norepinephrine transporters. The aim of the present study was to investigate the effects of venlafaxine on the depressive-like behaviors and serum estradiol levels in female rats following ovariectomy (OVX) and the possible roles of EPO-induced signaling pathways. Venlafaxine (10mg/kg/day) was orally administered to OVX rats over a period of 4weeks using two different treatment regimens: either starting 24h or 2weeks after OVX. Venlafaxine showed a superior efficacy in inducing antidepressant-like effects after an acute treatment (24h post-OVX) than after the delayed treatment (2weeks post-OVX) and was characterized by a decreased immobility time in the forced swimming test. In parallel, venlafaxine induced EPO and EPO receptor mRNA expression and increased levels of phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 5, and phospho-extracellular signal-regulated kinase 1/2 in the hippocampus of OVX rats. Meanwhile, rats exhibited a marked reduction in the hippocampal Bax/Bcl2 ratio, caspase-3 activity, and tumor necrosis factor alpha levels after venlafaxine treatment. Venlafaxine also increased the hippocampal brain-derived neurotrophic factor and serum estradiol levels. Based on these findings, venlafaxine exerts a neuroprotective effect on OVX rats that is at least partially attributed to the activation of EPO/EPOR/JAK2 signaling pathways, anti-apoptotic activities, anti-inflammatory activities, and neurotrophic activities, as well as an increase in serum estradiol level. Graphical Abstract ᅟ.

Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice

Many epidemiological and clinical studies have demonstrated a strong comorbidity between anxiety and depression, and a number of experimental studies indicates that the dopamine transporter (DAT) is involved in the pathophysiology of anxiety and depression. However, studies using laboratory animals have yielded inconclusive results. The aim of the present study was to examine the effects of DAT manipulation on anxiety- and depression-like behaviors in mice. For this purpose, animals were stereotaxically injected with DAT siRNA-expressing lentiviral vectors (siDAT) in the caudate putamen (CPu) or in the nucleus accumbens (Nacc) and the behavioral outcomes were assessed using the open-field (OF), elevated-plus maze (EPM), light-dark box (LDB), sucrose preference (SPT), novelty suppressed feeding (NSF), and forced-swim (FST) tests. The results showed that in the Nacc, but not in the CPu, siDAT increased the time spent at the center of the arena and decreased the number of fecal boli in the OF test. In the EPM and LDB tests, Nacc siDAT injection increased the entries and time spent on open arms, and increased the time spent in the light side of the box, respectively, suggesting an anxiolytic-like activity. In addition, siDAT, in the Nacc, induced significant antidepressant-like effects, evidenced by increased sucrose preference, shorter latency to feed in the NSF test, and decreased immobility time in the FST. Most importantly, Pearson’s test clearly showed significant correlations between DAT mRNA in the Nacc with anxiety and depression parameters. Overall, these results suggest that low DAT levels, in the Nacc, might act as protective factors against anxiety and depression. Therefore, targeting DAT activity might be a very attractive approach to tackle affective disorders.

Effects of ovarian hormones on emotional behaviors in dopamine D3 receptor knockout mice

Ovarian hormones reportedly have beneficial effects on affective behaviors. However, the functions of ovarian hormones in neurotransmitter signaling must be identified to understand their role in anxiety and depression. Several studies have provided evidence of the relationship between ovarian hormones and the dopaminergic system, but the interaction between ovarian hormones and dopamine D3 receptor (DRD3) is poorly understood. The aim of the present study was to examine the role of DRD3 in the anxiety-like and depression-like behavioral changes induced by estrogen and progesterone. We subjected D3 receptor knockout (D3KO) and wild-type (WT) mice to a series of behavioral tests. Mice were ovariectomized 4 weeks before testing, and we randomly administered 17β-estradiol (E2, 0.2 mg/kg), progesterone (P4, 10 mg/kg), E2 (0.2 mg/kg) plus P4 (10 mg/kg) or vehicle (VEH, corn oil, 0.2 ml) subcutaneously daily for 9 consecutive days, starting 4 days before the testing day. On the testing day, the mice were injected 30 min prior to behavioral testing. Compared with WT mice in the same treatment group, D3KO mice displayed hyperactivity in the light-dark box test (LDBT) but lower activity in the open field test (OFT). In addition, D3KO mice but not their WT littermates showed behavioral changes after E2 treatment compared with those after VEH treatment in the LDBT only. In depression tests, D3KO-VEH mice displayed significantly longer immobility times than did WT-VEH mice. In addition, only D3KO mice exhibited an obvious decrease in immobility time after E2 and P4 administration. These results indicate that the anxiolytic and antidepressant effects of ovarian hormones can be influenced by DRD3 expression and that DRD3 knockout may induce varying sensitivities to ovarian hormones that depend on various factors, including test paradigms and experiences in animal models. Our research provides a novel insight, i.e., DRD3 may play a role in the efficacy of hormone therapy.

Ciliary neurotrophic factor is a key sex-specific regulator of depressive-like behavior in mice

Ciliary neurotrophic factor (CNTF) is produced by astrocytes and promotes neurogenesis and neuroprotection. Little is known about the role of CNTF in affective behavior. We investigated whether CNTF affects depressive- and anxiety-like behavior in adult mice as tested in the forced swim, sucrose preference and elevated-T maze tests. Female wild type CNTF+/+ mice more readily developed behavioral despair with increased immobility time and decreased latency to immobility in the forced swim test than male CNTF+/+ littermates. The lack of CNTF in CNTF-/- mice had an opposite effect on depressive-like behavior in female mice (reduced immobility time and increased sucrose preference) vs. male mice (increased immobility time). Female wildtype mice expressed more CNTF in the amygdala than male mice. Ovariectomy increased CNTF expression, as well as immobility time, which was significantly reduced in CNTF-/- mice, suggesting that CNTF mediates overiectomy-induced immobility time, possibly in the amygdala. Progesterone but not 17-β estradiol inhibited CNTF expression in cultured C6 astroglioma cells. Progesterone treatment also reduced CNTF expression in the amygdala and decreased immobility time in female CNTF+/+ but not in CNTF-/- mice. Castration did not alter CNTF expression in males nor their behavior. Lastly, there were no effects of CNTF on the elevated T-maze, a behavioral test of anxiety, suggesting that a different mechanism may underlie anxiety-like behavior. This study reveals a novel CNTF-mediated mechanism in stress-induced depressive-like behavior and points to opportunities for sex-specific treatments for depression, e.g. progesterone in females and CNTF-stimulating drugs in males.

Bafilomycin A1 alleviates depression‑like symptoms in chronic unpredictable mild stress rats.

Major depression is a multifactorial disease. Emerging evidence has suggested that autophagy is involved in the pathological process of depressive disorders. BafilomycinA1 (BafA1), is an inhibitor of vacuolar H+‑ATPase that is frequently used at high concentrations to block late‑phase autophagy. However, whether BafA1 has antidepressant effects remains to be elucidated. The current study aimed to evaluate the antidepressant effects of BafA1 in rats with chronic unpredictable mild stress (CUMS) and its potential mechanism. The CUMS animal model was established. The sucrose preference test, open‑field test (OFT) and forced swim test (FST) were applied to evaluate the depressive behavior. Synaptic plasticity‑associated proteins synaptophysin and postsynaptic density protein 95 were measured by western blotting and immunofluorescence. Apoptosis‑ and autophagy‑associated proteins in addition to pro‑inflammatory cytokines, including interleukin‑1β and tumor necrosis factor‑α, were detected by western blotting, reverse transcription‑quantitative polymerase chain reaction or ELISA. A 4‑week treatment period with BafA1 markedly ameliorated CUMS‑induced behavioral abnormalities, including increasing sucrose intake, improving locomotor activity in the OFT, and decreasing immobility time in the FST. In addition, treatment with BafA1 restored the dysregulation of synaptic plasticity and inhibited neuroinflammation in rats exposed to CUMS. Furthermore, BafA1 decreased the levels of apoptosis‑ and autophagy‑associated proteins induced by CUMS. The present study demonstrated that BafilomycinA1 resulted in antidepressant effects in rats, which may be mediated by the reversal of apoptosis, autophagy and neuroinflammation in the hippocampus.

Crocin, a natural product attenuates lipopolysaccharide-induced anxiety and depressive-like behaviors through suppressing NF-kB and NLRP3 signaling pathway

Depression is one of the foremost psychological illness which is closely leagued with inflammation. Crocin is a natural product that exhibits both anti-inflammatory and anti-oxidant activities. However, little is known about anti-inflammatory mechanisms of crocin on LPS-induced anxiety and depressive-like behaviors. The objective of this study is emphasized on neuroprotective role of crocin against LPS-induced anxiety and depressive-like behaviors in mice. It is observed that crocin inhibited LPS-induced production of NO, TNF-α, IL-1β and ROS in BV-2 microglial cells. Moreover, crocin significantly declined the expression of iNOS, NF-κB p65 and CD16/32 (M1 marker), as well as elevated the expression of CD206 (M2 marker) in BV-2 cell line with decreased LPS-induced anxiety and depressive-like behaviors by improved locomotor activity, reduced sucrose intake, and decreased immobility time in forced swim and tail suspension test in Kunming mice. Expression of NLRP3, ASC and caspase-1 by i.p administration of LPS found to be neutralized with reduction in level of IL-1β, IL-18 and TNF-α in mouse hippocampus. In conclusion, these results suggested that crocin as a potential therapeutic candidate for neuro-inflammation and depressive-like behaviors induced by LPS. The effect was found to be due to inhibition of NLRP3 inflammasome and NF-κB and its promoted M1 to M2 phenotypic conversion of microglia.

EVALUATION OF ANTI-STRESS ACTIVITY OF ETHANOLIC EXTRACTS OF TERMINALIA CATAPPA L. IN SWISS ALBINO MICE

Objective: The aim of the study was to evaluate the anti-stress activity of ethanolic extract of Terminalia catappa L. in Swiss albino mice. Methods: The extract used in this study was prepared by Soxhlet extraction of fresh dried leaves of T. catappa L. using ethanol as an extraction solvent. Stress is involved in the pathogenesis of a variety of diseases including hypertension, peptic ulcer, immunodepression, reproductive dysfunction, and behavior disorder. Overload of stress increases free radicals, produces damage to neuronal receptors and a variety of tissues. In this experimental research study two models, namely, forced swim test (FST) and tail suspension test (TST) were used for the screening of anti-stress activity. 50, 100, and 200 mg/kg ethanolic extracts of T. catappa L. were given orally, while 2mg/kg of Diazepam which acts as a standard was given intraperitoneally. The data obtained were analyzed by one-way ANOVA, followed by Dunnett’s test. p<0.05 was considered to be significant. Result: The entire three test groups of the ethanolic extract of leaves of T. catappa L. showed decrease in immobility time in both FST (immobility for 42.5±3.5 s and mobility at 197.5±3.5 s) against diazepam (immobility 82.6±4.17 s and mobility at 157.3±4.17 s) and TST (92±2.28 s and mobility at 148±2.28) when compared against control as well as against diazepam (116.3±2.73 s and mobility at 123.6±2.73) which was used as a standard. Conclusion: There is substantial evidence that flavonoids play an active role in providing anti-stress activity. This study is an attempt to find out the alternative medication for treating chronic stress with single medication which was shown a beneficial effect in animal models, may be useful for curing symptoms of stress.

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats.

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats.

Behavioral disturbances are observed in most patients suffering from diabetes. According to some evidence, pro-inflammatory cytokines have a key role both in diabetes and behavioral disorders, such as anxiety and depression. In this study, the effect of chronic administration of loganin, as a bioflavonoid, was investigated on pro-inflammatory cytokines and depression- and anxiety-like behaviors in streptozotocin-induced diabetes in male Wistar rats. Blood levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay method. Depression- and anxiety-like behaviors were evaluated by forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT), respectively. Body weight was also measured before the interventions and after the experiments in all groups. Our findings show that loganin-treated animals had significantly lower serum concentrations of IL-6 and TNF-α compared with the diabetic group. In the EPM test, loganin treatment significantly increased the percentage of the open arm time and open arm entries. Moreover, loganin treatment significantly decreased the grooming time and restored distance traveled and center crossing in the OFT. However, it decreased immobility time in the FST. Loganin treatment also significantly restored body weight gain and attenuated blood glucose changes in the diabetic rats. These results indicate that loganin possibly alleviates depression- and anxiety-like behaviors associated with diabetes through lowering the blood glucose and pro-inflammatory cytokine levels. More research is required to show the exact mechanism of antidepressant and anxiolytic effects of loganin in diabetes.

Anti-stress effects of human placenta extract: possible involvement of the oxidative stress system in rats

BackgroundHuman placenta hydrolysate (hPH) has been utilized to improve menopausal, fatigue, liver function. Its high concentration of bioactive substances is known to produce including antioxidant, anti-inflammatory and anti-nociceptive activities. However, its mechanisms of stress-induced depression remain unknown.MethodsThe present study examined the effect of hPH on stress-induced depressive behaviors and biochemical parameters in rats. hPH (0.02 ml, 0.2 ml or 1 ml/rat) was injected intravenously 30 min before the daily stress session in male Sprague-Dawley rats exposed to repeated immobilization stress (4 h/day for 7 days). The depressive-like behaviors of all groups were measured by elevated plus maze (EPM) and forced swimming test (FST). After the behavior tests, brain samples of all groups were collected for the analysis of glutathione peroxidase (GPx) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining.ResultsTreatment with hPH produced a significant decrease of immobility time in the FST compared to the controls. Additionally, hPH treatment elicited a slightly decreasing trend in anxiety behavior on the EPM. Furthermore, hPH increased the level of GPx protein in the hippocampus, and decreased the expression of NADPH-d in the paraventricular nucleus (PVN).ConclusionThis study demonstrated that hPH has anti-stress effects via the regulation of nitric oxide (NO) synthase and antioxidant activity in the brain. These results suggest that hPH may be useful in the treatment of stress-related diseases such as chronic fatigue syndrome.

A novel PDE9 inhibitor WYQ-C36D ameliorates corticosterone-induced neurotoxicity and depression-like behaviors by cGMP-CREB-related signaling.

Major depressive disorder (MDD) is a mental disease characterized by depressed mood, lifetime anxiety, and deficits of learning and memory. Inhibition of phosphodiesterase 9 (PDE9) has been reported to improve rodent cognitive and memory function. However, the role of PDE9 in MDD, in particular its manifestations of depression and anxiety, has not been investigated. We examined the protective effects of WYQ-C36D (C36D), a novel PDE9 inhibitor, against corticosterone-induced cytotoxicity, pCREB/CREB and BDNF expression by cell viability, and immunoblot assays in HT-22 cells. The potential effects of C36D at doses of 0.1, 0.5, and 1mg/kg on stress-induced depression- and anxiety-like behaviors and memory deficits were also examined in mice. C36D significantly protected HT-22 cells against corticosterone-induced cytotoxicity and rescued corticosterone-induced decreases in cGMP, CREB phosphorylation, and BDNF expression. All these effects were otherwise blocked by the PKG inhibitor Rp-8-Br-PET-cGMPS (Rp8). In addition, when tested in vivo in stressed mice, C36D produced antidepressant-like effects on behavior, as shown by decreased immobility time both in the forced swimming and tail suspension tests. C36D also showed anxiolytic-like and memory-enhancing effects in the elevated plus-maze and novel object recognition tests. Our results show that inhibition of PDE9 by C36D produces antidepressant- and anxiolytic-like behavioral effects and memory enhancement by activating cGMP/PKG signaling pathway. PDE9 inhibitors may have the potential as a novel class of drug to treat MDD.

Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy.

BackgroundMajor depressive disorders are characterized by their severity and long‐lasting symptoms, which make such disorders highly disabling illnesses. Unfortunately, 50% of major depressive patients experience relapses, perhaps partly because drug research has been performed only in animal models that screen for antidepressant drugs that appear to only ameliorate acute depression symptoms. The bilateral olfactory bulbectomy (OBX) animal model presents the advantage of mimicking the symptoms of chronic depression by means of brain surgery. Adenosine purinergic receptors A2A (A2AR) have been the target of interest in the field of psychiatric diseases. This study aimed to show which A2A receptor ligands exert antidepressive‐like effects in the OBX rat model.MethodsForty Sprague‐Dawley male rats were divided into four groups: control, OBX + vehicle, OBX + ZM 241385, and OBX + adenosine groups. Pharmacological treatment was administered for 14 days, and the rats were examined via the forced swim test (FST), open field test (OFT), and sucrose preference test (SPT).ResultsThe OBX + ZM 241385 group exhibited decreased immobility time in the FST, decreased isolation time in the OFT, and reversed anhedonia behavior in the SPT compared to the vehicle group. However, no significant differences for adenosine treatment were found.Conclusions ZM 241385 administration (2 mg/kg i.p.) restored behavioral changes associated with OBX‐induced depression.