Involvement of mTOR‐related signaling in antidepressant effects of Sophoraflavanone G on chronically stressed mice

SophoraflavanoneG (SG), an important prenylated flavonoid isolated from Sophoraalopecuroides.L, is effective for many illnesses. The present study was designed to investigate whether the compound could reverse depressive‐like symptoms and investigate its possible mechanisms. Chronic Unpredictable Mild Stress (CUMS) mice were treated with fluoxetine and SG. The immobility time in forced swimming test (FST) and tail suspension test (TST) were recorded. The levels of pro‐inflammatory cytokines and neurotransmitters in the hippocampus were evaluated. Furthermore, the protein expressions of PI3K, AKT, mTOR, p70S6K, BDNF, and Trkb in hippocampus were detected. Rapamycin, the selective mTOR inhibitor, was used to estimate the potential mechanism. As a result, after 7 days of SG treatment, the immobility time in FST and TST was declined obviously. The levels of IL‐6, IL‐1β, and TNF‐α in the hippocampus were significantly reduced, and the quantity of 5‐HT and NE was raised considerably in SG‐treated group compared with the CUMS‐exposed group. Additionally, SG could up‐regulate the expressions of PI3K, AKT, mTOR, 70S6K, BDNF, and Trkb. The blockade of mammalian target of rapamycin signaling blunted the antidepressant effect and reversed the up‐regulation of BDNF expression caused by SG. These findings suggested that SG treatment alleviated depressive‐like symptoms via mTOR‐mediated BDNF/Trkb signaling.     

Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain‐derived neurotrophic factor

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant‐like effects. We observed that SD aggravated the anxiety‐like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant‐like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant‐like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.     

Brain‐derived Neurotrophic Factor Signaling Mediates the Antidepressant‐like Effect of the Total Flavonoids of Alpiniae Oxyphyllae Fructus in Chronic Unpredictable Mild Stress Mice

The present study verified the antidepressant‐like effects of the total flavonoids of Alpinia oxyphylla Miq. (AOF) using the chronic unpredictable mild stresses paradigm and explored the mechanism that underlies antidepressant‐like effects of AOF in mice. Previous research has shown that tropomyosin‐related kinase B (TrkB) receptor‐mediated extracellular regulated protein kinases (ERK) signaling pathways participate in depression pathophysiology. Therefore, we aimed to explore whether AOF improved depression‐like behaviors by increasing activity of ERK pathways mediated by TrkB. Results showed that AOF significantly reduced the immobility time in the forced swimming test and increased the sucrose preference in sucrose preference test. In addition, decreased phosphorylated cyclic adenosine monophosphate response element‐binding protein (pCREB)/CREB, pERK/ERK, and pTrkB/TrkB levels in the hippocampus induced by chronic unpredictable mild stresses were reversed by intragastric administration of AOF. Results suggested that AOF increased pCREB/CREB, pERK/ERK, and pTrkB/TrkB levels by acting on the TrkB receptor. To verify this hypothesis, mice were pretreated with the TrkB inhibitor K252a (or 0.1% dimethyl sulfoxide, intraperitoneally, 2 weeks), before the intragastric administration of AOF. This resulted in an absence of antidepressant‐like effects, as well as no activation of pERK/pCREB/BDNF signaling pathways. Results demonstrated that AOF might exert antidepressant‐like effects by targeting TrkB receptor‐mediated pERK/pCREB/BDNF signal systems, which could help to identify the AOF receptor. Copyright © 2016 John Wiley & Sons, Ltd.     

Rapid antidepressant‐like effect of Fructus Aurantii depends on cAMP‐response element binding protein/Brain‐derived neurotrophic facto by mediating synaptic transmission

Several studies reported the relative antidepressant effects of Fructus Aurantii (FRA) with repeated treatment, the rapid antidepressant effects of FRA and the underlying mechanisms remained unclear. We, therefore, examined the rapid antidepressant actions of FRA in behavioral tests in mice and tested the underlying molecular mechanisms. We found FRA, like ketamine, reversed the behavioral deficits both in lipopolysaccharide(LPS)‐induced and learned helplessness (LH) models at 1 day after a single administration. FRA was also capable of increasing the expressions of protein kinase A/cAMP‐response element‐binding protein/brain‐derived neurotrophic factor (PKA/CREB/BDNF) signaling in hippocampus. Consistent with ketamine, FRA up‐regulated the expressions of GABAergic receptor (GAD67) and glutamatergic receptor 1 (GluR1) in mouse hippocampus both exposed to LPS and LH. Moreover, synaptic proteins such as postsynaptic density‐95 (PSD95) and synapsin1 were also up‐regulated by a single dose of FRA both in LH and LPS models, like ketamine. Finally, metadoxine (an antagonist of CREB) inhibited the antidepressant effects of FRA in tail suspension test (TST) and forced swimming test (FST) in LPS‐induced mice, which also blocked the phosphorylation of CREB and the expressions of neurotransmitters and synaptic molecules. Therefore, FRA had rapid antidepressant effects, which depended on PKA/CREB/BDNF pathway, subsequently regulated the downstream synaptic transmission.     

Inulin‐Type Oligosaccharides Extracted from Yacon Produce Antidepressant‐Like Effects in Behavioral Models of Depression

Yacon (Smallanthus sonchifolius), a traditional food in the Andean diet, is attracting global attention for its medicinal properties, which are mainly because of its high content of non‐digestible oligosaccharides. The purpose of this study is to evaluate the antidepressant‐like effects of inulin‐type oligosaccharides extracted from yacon (YOs) in behavioral models of depression. Behavioral despair models in mice including the tail suspension test (TST) and the forced swimming test (FST) were used to determine the effects of acute YOs administration. The locomotor activity was also explored to eliminate any false‐positive activity. In addition, to further investigate the antidepressant‐like effects of subchronic YOs administration, the learned helplessness (LH) paradigm in rats was performed. The results demonstrated that YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reduced the immobility time in the mouse TST and FST in a U‐shaped, dose‐dependent manner, and showed no stimulatory effect on the locomotor activity. Furthermore, subchronic YOs (25, 50, or 100 mg/kg, p.o.) treatment significantly reversed the escape deficits in LH rats, including an increased number of escape failures and prolonged escape latency. These findings suggest that the inulin‐type oligosaccharides extracted from yacon may be a prospective natural source for antidepressants. Copyright © 2016 John Wiley & Sons, Ltd.     

Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant‐Like Effects in Olfactory Bulbectomized Mice

Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain‐derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin‐related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5‐bromo‐2′‐deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX‐induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal‐regulated kinase and cyclic AMP‐responsive element‐binding protein after 3 h. The present data indicate that magnolol exerts antidepressant‐like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin‐related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd.     

Schisandra chinensis ameliorates depressive‐like behaviors by regulating microbiota‐gut‐brain axis via its anti‐inflammation activity

The present study aimed to examine the antidepressant actions of the composition fractions of Schisandra chinensis using LPS‐induced mice. Animals were treated with total extracts (SCE), lignans (SCL), polysaccharides (SCPS), and essential oil (SCVO), and then subjected to behavioral tests. The forced swimming test (FST) and tail suspension test (TST) were used as predictive animal models of antidepressant activity. Total extracts and lignans significantly decreased the duration of immobility in FST and TST. We found that treatment with SCE and SCL could significantly decrease the levels of pro‐inflammatory cytokines both in the periphery and central nervous system (CNS). This was confirmed by the histopathological examination of the colon. The RT‐PCR results demonstrated that SCE and SCL could greatly inhibit the TLR4/NF‐κB/IKKα signaling pathway. In addition, the concentrations of Butyric acid and Propionic acid were upregulated by the administration, and the decreased diversity of intestinal microbiota and alterations of the relative proportions of Bacteroidetes and Firmicutes phylum members, Barnesiella and Lactobacillus genus members in LPS‐induced mice were restored as well. All results suggested that lignans is the effective fraction of S.chinensis to ameliorating depressive disorders, which its anti‐inflammation activity possibly involved in the bidirectional connection between gut microbiota and brain.     

Terpenoid content of Valeriana wallichii extracts and antidepressant‐like response profiles

Three extracts of Valeriana wallichii DC (Valerianaceae) rhizome and fluoxetine were studied for antidepressant‐like activity in two behavioral models, namely the forced swim test (FST) and the tail suspension test (TST). Fluoxetine as well as methanolic and aqueous extracts of V. wallichii induced monophasic dose‐related decrements in immobility times in both tests. However, the aqueous‐ethanolic fraction induced a biphasic dose‐response profile since it produced a graded effect up to 200 mg/kg but the highest dose (250 mg/kg) was inactive in the FST. This extract also exhibited significantly reduced activity at 200 mg/kg compared to lower doses in the TST. The highest doses of aqueous‐ethanolic extract also reduced locomotor activity which will have led to a negative functional interaction with antidepressant‐like effects. Qualitative phytochemical analysis revealed that the aqueous‐ethanolic extract of V. wallichii was the only separated rhizome fraction containing terpenoids. Furthermore, since the methanolic and aqueous extracts were active in the tests, it is suggested that the antidepressant‐like action of this herbal plant is not contingent upon its terpenoid constituents. Copyright © 2009 John Wiley & Sons, Ltd.     

Antidepressant effects of dammarane sapogenins in chronic unpredictable mild stress‐induced depressive mice

Depression is a common, dysthymic, and psychiatric disorder, resulting in enormous social and economic burden. Dammarane sapogenins (DS), an active fraction from oriental ginseng, has shown antidepressant‐like effects in chronic restraint rats and sleep interruption‐induced mice, and the present study aimed to further confirm the antidepressant effects of DS in a model of chronic unpredictable mild stress (CUMS) and to explore the underlying mechanism. Oral administration of DS (20, 40, and 80 mg/kg) markedly improved depressant‐like behaviors, increasing the sucrose intake in the sucrose preference test and reducing the latency in the novelty‐suppressed feeding test, and decreasing the immobility time in both the tail suspension and forced swimming tests, compared with the CUMS mice. Biochemical analysis of brain tissue and serum showed that DS treatment restored the decreased hippocampal neurotransmitter concentrations of serotonin, dopamine, norepinephrine (noradrenaline), and gamma‐aminobutyric acid, and decreased the elevated of serum hormone levels (corticotrophin releasing factor, adrenocorticotrophic hormone, and corticosterone) induced by CUMS. Our findings confirm that DS exerts an antidepressant‐like effect in the CUMS model of depression in mice, and suggest it may be mediated by regulation of neurotransmitters and hypothalamic–pituitary–adrenal axis.     

高度富集黄酮类成分的贯叶连翘提取物抗抑郁作用

目的探讨贯叶连翘提取物中高度富集的黄酮类成分的抗抑郁作用。方法采用小鼠强迫游泳实验、小鼠悬尾实验、开野实验和拮抗利血平所致的体温降低实验,分别以小鼠不动时间、自主活动数和体温下降值作为评价指标。结果在强迫游泳和悬尾实验中,40,80,160,240mg/kg剂量组贯叶连翘提取物均能显著缩短小鼠不动时间,20mg/kg剂量组无显著性差异;开野实验结果表明给药后小鼠的自主活动不同程度地减少;在利血平拮抗实验中,30,60,120mg/kg剂量组在3h,4h和5h各时间点体温下降值与模型对照组相比有显著性差异,240和480mg/kg两剂量组在各测定时间点体温下降值与模型对照组相比均有显著性差异。结论高度富集总黄酮的贯叶连翘提取物(弃除贯叶金丝桃素)有抗抑郁作用。     

芍药苷抗抑郁作用的实验研究

目的研究芍药苷的抗抑郁作用,并对其作用机制进行初步探讨。方法采用小鼠强迫游泳、小鼠悬尾实验和体外培养PCI2细胞的方法,观察芍药苷对小鼠游泳不动时间、悬尾不动时间的影响以及对皮质酮损伤PCI2细胞存活率的影响。结果芍药苷连续给药一周后,能明显缩短小鼠在行为学实验中的不动状态时间,并能拮抗皮质酮诱导的神经毒作用,提高PCI2细胞的存活率。结论芍药苷具有明显的抗抑郁作用,其机制可能与细胞保护作用有关。     

Preventive Effects of Ginseng Total Saponins on Chronic Corticosterone‐Induced Impairment in Astrocyte Structural Plasticity and Hippocampal Atrophy

To further explore the underlying antidepressant mechanism of ginseng total saponins (GTS), this study observed the effects on hippocampal astrocyte structural plasticity and hippocampal volume in the corticosterone‐induced mouse depression model. Corticosterone (20 mg/kg/day) was administered subcutaneously for 5 weeks, and GTS (12.5, 25, and 50 mg/kg/day; namely GTSL, GTSM, and GTSH) or fluoxetine (10 mg/kg/day) were given intragastrically during the last 3 weeks. On day 33 and day 34, depression‐like behavior was observed via a forced swimming test and a tail suspension test, respectively. At 6 h after the last dose of corticosterone (day 35), all mice were sacrificed followed by serum corticosterone assays, stereological analysis of hippocampal glial fibrillary acidic protein‐positive (GFAP⁺) astroctyes and hippocampal volume, and hippocampal glycogen tests. Results showed that all doses of GTS ameliorated depression‐like behavior and the decrease in hippocampal glycogen without normalizing hypercortisolism. Moreover, GTSH and GTSM reversed the corticosterone‐induced reduction in the total number of hippocampal GFAP⁺ astrocytes and hippocampal volume. Additionally, GTSH alleviated the diminished protrusion length and somal volume of GFAP⁺ astrocytes induced by corticosterone. These findings imply that the effects of GTS on corticosterone‐induced depression‐like behavior may be mediated partly through the protection to hippocampal astrocyte structural plasticity. Copyright © 2017 John Wiley & Sons, Ltd.     

酸枣仁合欢方抗抑郁有效部位的研究

目的 以药效学方法筛选酸枣仁合欢方的抗抑郁有效部位.方法 采用小鼠强迫游泳实验、小鼠悬尾实验、空场实验和拮抗利血平所致的体温降低实验,比较总皂苷和总黄酮部位的抗抑郁药效.结果 在小鼠悬尾实验和游泳实验中,总皂苷组与模型组比较能显著缩短小鼠不动时间,表现出抗抑郁作用;总黄酮组虽能缩短小鼠不动时间,但无统计学意义(P＞0.05).空场实验表明各组间小鼠自主活动无显著性差异.在利血平拮抗实验中,总皂苷组在4h时可显著拮抗小鼠体温下降(P＜0.05).结论 通过抗抑郁药效学实验结果,初步确定总皂苷为酸枣仁合欢方的有效部位.     

淫羊藿提取物抗抑郁作用研究

目的研究淫羊藿提取物的抗抑郁作用。方法采用行为绝望模型悬尾试验(TST)和强迫游泳试验(FST)研究淫羊藿提取物对小鼠行为、脑内单胺氧化酶A(M AO-A)、单胺氧化酶B(M AO-B)活性与肝脏中M AO-A和M AO-B活性及丙二醛(M DA)水平的影响;采用利血平拮抗模型探讨淫羊藿提取物可能存在的抗抑郁作用途径。结果淫羊藿提取物(25、50、100、200 m g/kg)能显著缩短TST和FST小鼠悬尾和游泳不动时间,显著抑制TST小鼠脑和肝组织M AO-A和M AO-B活性,逆转肝组织M DA水平的升高。淫羊藿提取物对利血平所致小鼠体温的下降无明显改善作用。结论淫羊藿提取物具有一定抗抑郁作用。     

绞股蓝提取物抗抑郁活性研究

目的考察绞股蓝提取物抗抑郁活性。方法通过3种动物模型,即小鼠悬尾实验(TST)、强迫游泳实验(FST)和开场实验(OFT)模型,首次测试绞股蓝75%乙醇提取物(醇提物,JE)及其水提物(JW)的抗抑郁活性。结果 JE(2.5,5 g/kg)可使小鼠在TST及FST的不动时间均显著性缩短(P<0.05),呈现出良好的量效关系,且与阳性药盐酸氟西汀(FH)相比无显著性差异(P>0.05),而JW(2.5,5 g/kg)对小鼠在TST及FST的不动时间均无显著性差异(P>0.05);各组小鼠OFT穿格次数比较,均无显著性差异(P>0.05)。结论首次证实绞股蓝醇提物具有抗抑郁活性,且与FH的作用相当,而其水提物在既定给药方案下无抗抑郁活性。     

The Antidepressant Effects of Ginseng Total Saponins in Male C57BL/6 N Mice by Enhancing Hippocampal Inhibitory Phosphorylation of GSK‐3β

Ginseng total saponins (GTS) are principal bioactive ingredients of Panax ginseng. In this study, we investigated the antidepressant effect of GTS on the corticosterone‐induced mouse depression model and explored the underlying mechanism. Corticosterone (20 mg kg^?1 d^?1) was subcutaneously administered for 22 d to induce the model, before doses of GTS (12.5, 25, and 50 mg kg^?1 d^?1) or fluoxetine (10 mg kg^?1 d^?1) were subsequently given by gavage. On day 20 and 21, depression‐like behavior was observed via a forced swimming test and a tail suspension test respectively. At 6 h after the last dose of corticosterone (day 22), all mice were sacrificed followed by serum corticosterone assays and Western blot analysis. The results showed that GTS (25 and 50 mg kg^?1 d^?1) treatments relieved depression‐like behavior without altering the elevated serum corticosterone levels. Furthermore, GTS treatments raised the down‐regulated levels of hippocampal glycogen synthase kinase‐3β (GSK‐3β) inhibitory phosphorylation. In contrast, fluoxetine (10 mg kg^?1 d^?1) treatment reversed the increased corticosterone level and had no effect on the decreased GSK‐3β inhibitory phosphorylation. These findings confirmed the antidepressant effect of GTS in the corticosterone‐induced mouse depression model. Enhancing GSK‐3β inhibitory phosphorylation may be one of the underlying mechanisms. Copyright © 2013 John Wiley & Sons, Ltd.     

Kaempferide prevents cognitive decline via attenuation of oxidative stress and enhancement of brain‐derived neurotrophic factor/tropomyosin receptor kinase B/cAMP response element‐binding signaling pathway

Kaempferide (KF) is a compound of flavonoids from Alpinae oxyphylla Miq, and the herb itself is used as a classical tonic agent. This paper aims to investigate the effects of KF on cognitive function impairment and neurodegeneration in the mouse model of Alzheimer's disease induced by intracerebroventricular (ICV) injection of Aβ_1–42. The mice were treated with KF at doses of 0.02 and 0.2 mg/kg/day (ICV) for five consecutive days after Aβ_1–42 exposures. The behavioral test results showed that KF could prevent cognitive decline in mice induced by Aβ_1–42 as assessed by the locomotor activity test, Y‐maze test, and Morris water maze test. Furthermore, the activities of superoxide dismutase and malondialdehyde in the hippocampus and cerebral cortex were elevated by KF administration. Results of hippocampus slices showed that neurons were integrated and regularly arranged in the groups, which were administered along with KF. In addition, we found KF could boost brain‐derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element‐binding (CREB) protein signal in the hippocampus. All results illustrated that KF could exert neuroprotective effects at least partly through alleviating oxidative stress and enhancing the BDNF/TrkB/CREB pathway in Aβ_1–42‐induced mice.     

小柴胡汤抗抑郁作用研究

目的:观察小柴胡汤的抗抑郁作用.方法:本实验将小鼠随机分成5组,即小柴胡汤高中低剂量组( 27,18,9g·kg -1剂量组,ig每天1次,连续给药7d)、盐酸氟西汀组(20 mg·kg-1)、空白对照组(分别ig给予等体积的生理盐水).采用小鼠悬尾、小鼠强迫游泳实验,以小鼠不动时间为指标来评价小柴胡汤的抗抑郁作用.结果:小柴胡汤高、中、低剂量组均能够显著缩短小鼠悬尾及强迫游泳不动时间.结论:小柴胡汤具有明显的抗抑郁作用.     

基于慢性轻度不可预知性温和型应激的C57BL/6N小鼠抑郁模型的建立与评价

目的：探索慢性轻度不可预知性温和型应激(CUMS)法建立抑郁症C57BL/6N小鼠模型的条件,观察不同时点该模型行为学变化,对该模型进行评价和优化。方法：对C57BL/6N小鼠进行连续8周的CUMS应激来诱导其抑郁状态。分别在造模3、5、8周时通过糖水偏好实验(SPT)、旷场实验(OFT)、强迫游泳实验(FST)、悬尾实验(TST)等行为学实验,观察小鼠抑郁样行为的改变。结果：与对照组相比,发现各时点CUMS组小鼠一般状态均较差,出现毛发脱落、体型瘦小、活动减少等;造模3、5、8周时均出现糖水偏好率下降,FST和TST不动时间的延长,OFT垂直运动次数减少等,提示CUMS组小鼠出现快感缺失、绝望感及探索能力下降;造模8周时出现OFT水平运动总路程缩短、运动速度减慢,提示CUMS组小鼠出现了自发运动能力下降。结论：CUMS应激可以成功建立C57BL/6N小鼠抑郁模型,并且随着应激时间的延长,C57BL/6N小鼠的抑郁表现逐渐加重。     

Antidepressant-like action of the bark ethanolic extract from Tabebuia avellanedae in the olfactory bulbectomized mice

Ethnopharmacological relevance

Tabebuia avellanedae Lorentz ex Griseb is a plant employed in tropical America folk medicine for the treatment of several diseases, including depressive disorders.

Aim of the study

To investigate the ability of Tabebuia avellanedae ethanolic extract (EET) administered chronically to cause an antidepressant-like effect in the tail suspension test (TST), a predictive test of antidepressant activity, and to reverse behavioral (hyperactivity, anhedonic-like behavior and increased immobility time in the TST) and biochemical changes induced by olfactory bulbectomy (OB), a model of depression, in mice.

Materials and methods

Mice were submitted to OB to induce depressive-related behaviors, which were evaluated in the open-field test (hyperactivity), splash test (loss of motivational and self-care behavior indicative of an anhedonic-like behavior) and TST (increased immobility time). Phosphorylation levels of Akt, GSK-3β, ERK1/2 and CREB, as well as BDNF immunocontent, were evaluated in the hippocampus of bulbectomized mice or sham-operated mice treated for 14 days by p.o. route with EET or vehicle.

Results

EET (10 and 30 mg/kg) given 14 days by p.o route to mice reduced the immobility time in the TST without altering locomotor activity, an indicative of an antidepressant-like effect. EET per se increased both CREB (Ser¹³³) and GSK-3β (Ser⁹) phosphorylation (at doses of 10–30 and 30 mg/kg, respectively) in sham-operated mice. OB caused hyperactivity, loss of motivational and self-care behavior, increased immobility time in the TST and an increase in CREB and ERK1 phosphorylation, as well as BDNF immunocontent. EET abolished all these OB-induced alterations except the increment of CREB phosphorylation. Akt (Ser⁴⁷³) and ERK2 phosphorylation levels were not altered in any group.

Conclusions

EET ability to abolish the behavioral changes induced by OB was accompanied by modulation of ERK1 and BDNF signaling pathways, being a promising target of EET. Results indicate that this plant could constitute an attractive strategy for the management of depressive disorders, once more validating the traditional use of this plant.