左旋薄荷酮抗抑郁作用及机制研究

目的：研究左旋薄荷酮（MTN）的抗抑郁作用及可能机制。方法：以开野实验、强迫游泳实验、悬尾实验、糖水偏好实验对ICR小鼠进行行为学观察,探讨左旋薄荷酮对抑郁模型小鼠行为学的改善作用,同时检测小鼠血清皮质酮及皮质中糖皮质激素受体（GR）、脑源性神经营养因子（BDNF）含量的变化。结果：左旋薄荷酮15、30 mg·kg-1能显著缩短小鼠强迫游泳、悬尾不动时间,显著提高慢性不可预知温和刺激（CUMS）小鼠糖水偏好值,并能显著降低CUMS小鼠血清皮质酮含量、升高GR mRNA和BDNF的表达。结论：左旋薄荷酮具有抗抑郁作用,其抗抑郁机制可能与抑制下丘脑-垂体-肾上腺轴（HPA轴）过度活化、促进皮质BDNF的表达有关。     

Evaluation of antinociceptive and anti-inflammatory activity of hydromethanol extract of Cocos nucifera L.

Cocos nucifera L. (family: arecaceae) is generally straight unbranched plant, traditionally cultivated for its fruit (coconut) in home gardens. In the present study, anti-inflammatory and antinociceptive (analgesic) activity of hydromethanol extract of Cocos nucifera L. (HECN) was evaluated in animal models. HECN showed significant (p < 0.05) and dosedependent anti-inflammatory activity in carrageenan induced paw oedema models of inflammation and the result was comparable with the standard drug diclofenac. In addition, the extract also showed highly significant (p < 0.01) antinociceptive activity. HECN treated group showed increase in the reaction time in hot plate method and decrease the writhing induced by acetic acid in mice when compared with control group animal. The anti-inflammatory and antinociceptive activity observed in the present study could be attributed largely to the presence of its antioxidant phytoconstituents such as flavonoid, saponin and polyphenols.     

Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice

Objectives:

The present study was undertaken to investigate the effect of the ethanolic extract of Allium sativum L. (Family: Lilliaceae), commonly known as garlic, on depression in mice.

Materials and Methods:

Ethanolic extract of garlic (25, 50 and 100 mg/kg) was administered orally for 14 successive days to young Swiss albino mice of either sex and antidepressant-like activity was evaluated employing tail suspension test (TST) and forced swim test (FST). The efficacy of the extract was compared with standard antidepressant drugs like fluoxetine and imipramine. The mechanism of action of the extract was investigated by co-administration of prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABA_B agonist) and p-CPA (serotonin antagonist) separately with the extract and by studying the effect of the extract on brain MAO-A and MAO-B levels.

Results:

Garlic extract (25, 50 and 100 mg/kg) significantly decreased immobility time in a dose-dependent manner in both TST and FST, indicating significant antidepressant-like activity. The efficacy of the extract was found to be comparable to fluoxetine (20 mg/kg p.o.) and imipramine (15 mg/kg p.o.) in both TST and FST. The extract did not show any significant effect on the locomotor activity of the mice. Prazosin, sulpiride, baclofen and p-CPA significantly attenuated the extract-induced antidepressant-like effect in TST. Garlic extract (100 mg/kg) administered orally for 14 successive days significantly decreased brain MAO-A and MAO-B levels, as compared to the control group.

Conclusion:

Garlic extract showed significant antidepressant-like activity probably by inhibiting MAO-A and MAO-B levels and through interaction with adrenergic, dopaminergic, serotonergic and GABAergic systems.     

Antidepressant effects of a plant-derived flavonoid baicalein involving extracellular signal-regulated kinases cascade

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that baicalein (Bai), one plant-derived active flavonoid, exhibits neuroprotection against ischemic brain injury and stimulates the levels of phosphorylation of extracellular signal-regulated kinase (pERK) and brain-derived neurotrophic factor (BDNF) expression in vivo. In this study, the antidepressant-like effects of baicalein was investigated using acute and chronic animal models of depression. The results showed that acute application of Bai at doses of 1, 2 and 4 mg/kg by intraperitoneal injection (i.p.) significantly reduced the immobility time in the forced swimming test (FST) and tail suspending test (TST) of mice. In addition, the chronic application of Bai by i.p. for 21 d also reduced the immobility time and improved locomotor activity in chronic unpredictable mild stress (CMS) model rats. Furthermore, it was shown that Bai reversed the reduction of extracellular ERKs phosphorylation and the level of BDNF expression in the hippocampus of CMS model rats. These results suggest that Bai produce an antidepressant-like effect and this effect is at least partly mediated by hippocampal ERK-mediated neurotrophic action.     

Antidepressant-like effects of piperine and its derivative,antiepilepsirine

In the present study, antidepressant-like effects of piperine (PIP) and its derivative, antiepilepsirine (AES), were investigated in two depressive models: forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, the brain monoamine levels and monoamine oxidase A and B (MAO-A and MAO-B) activities were also determined. The research results for the first time indicated that after two weeks of chronic administration, PIP and AES at doses of 10–20 mg/kg significantly reduced the duration of immobility in both FST and TST, without accompanying changes in locomotor activity in the open-field test. But at the dose of 80 mg/kg, the antidepressant activity of both PIP and AES returned to the control level in the TST and FST. In the monoamine assay, chronic AES administration significantly elevated the dopamine level in striatum, hypothalamus and hippocampus, and also increased the serotonin level in the hypothalamus and hippocampus. In contrast, chronic treatment of PIP only enhanced the serotonin level in the hypothalamus and hippocampus but did not influence the dopamine level. Moreover, both PIP and AES showed no effects on level of noradrenaline in these brain regions. The MAO activity assay also indicated that PIP and AES showed a minor MAO inhibitory activity. In the present study, we demonstrated that the antidepressant-like effects of PIP and AES might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake. Antidepressant properties of PIP were supposed to be mediated via the regulation of serotonergic system, whereas the mechanisms of antidepressant action of AES might be due to its dual regulation of both serotonergic and dopaminergic systems.     

Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress

This study focused on the antidepressant potential of orcinol glucoside (OG) and its possible mechanisms of action. We established a depressed rat model using 3 consecutive weeks of chronic unpredictable mild stress (CUMS). The antidepressant-like effect of OG was revealed using the sucrose preference test, the open field test, the forced swimming test (FST), and the tail suspension test (TST). The activity of the hypothalamic–pituitary–adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations and mRNA expression of corticotrophin-releasing hormone (CRH) in the hypothalamus. The protein expression levels of brain-derived neurotrophic factor (BDNF) and total phosphorylated-ERK1/2 were detected by western blot. The results showed that OG treatment (1.5, 3, or 6 mg/kg) alleviated the depression-like behaviour of rats under CUMS, as indicated by the increased sucrose preference and the decreased immobility in both the FST and TST, although the rearing frequency in the open field test increased only in the group that received the lowest dose (1.5 mg/kg OG). Rats that received OG treatment exhibited reduced serum CORT levels and CRH mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by OG treatment. Moreover, OG treatment upregulated the protein levels of BDNF and phosphorylated-ERK1/2 in the hippocampus, even above control levels. Our findings suggest that OG improved depressive behaviour in CUMS rats by downregulating HPA axis hyperactivity and increasing BDNF expression and ERK1/2 phosphorylation in the hippocampus.     

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

In addition to its clinical antimanic effects, lithium also has efficacy in the treatment of depression. However, the mechanism by which lithium exerts its antidepressant effects is unclear. Our objective was to further characterize the effects of peripheral and central administration of lithium in mouse models of antidepressant efficacy as well as to investigate the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in these behaviors. We utilized the mouse forced swim test (FST) and tail suspension test (TST), intracerebroventricular (ICV) lithium administration, AMPA receptor inhibitors, and BS3 crosslinking followed by Western blot. Both short- and long-term administration of lithium resulted in robust antidepressant-like effects in the mouse FST and TST. Using ICV administration of lithium, we show that these effects are due to actions of lithium on the brain, rather than to peripheral effects of the drug. Both ICV and rodent chow (0.4% LiCl) administration paradigms resulted in brain lithium concentrations within the human therapeutic range. The antidepressant-like effects of lithium in the FST and TST were blocked by administration of AMPA receptor inhibitors. Additionally, administration of lithium increased the cell surface expression of GluR1 and GluR2 in the mouse hippocampus. Collectively, these data show that lithium exerts centrally mediated antidepressant-like effects in the mouse FST and TST that require AMPA receptor activation. Lithium may exert its antidepressant effects in humans through AMPA receptors, thus further supporting a role of targeting AMPA receptors as a therapeutic approach for the treatment of depression.     

Antidepressant-like effect of extract from Polygala paniculata: Involvement of the monoaminergic systems

Context: Polygala paniculata Linnaeus (Polygalaceae) has shown neuroprotective effects, but there is no report about its antidepressant potential.

Objective: The antidepressant-like effect of the hydroalcoholic extract from P. paniculata and some of the possible mechanisms involved in this effect were investigated in forced swimming test (FST).

Materials and methods: Mice received extract by oral route and were submitted to FST and open-field test. Animals were forced to swim and the total immobility time was registered (6-min period). A reduction in the immobility time is considered an antidepressant-like effect. In order to investigate the involvement of the monoaminergic systems, mice were treated with pharmacological antagonists before administration of the extract.

Results: The acute administration of the hydroalcoholic extract from P. paniculata produced an antidepressant-like effect, since it significantly reduced the immobility time in FST (0.01–30?mg/kg) as compared to control group, without changing locomotor activity. Pretreatment of mice with yohimbine (1?mg/kg, i.p., α₂-adrenoceptor antagonist), propranolol (1?mg/kg, i.p., β-adrenoceptor antagonist), SCH23390 (0.05?mg/kg, s.c., dopamine D₁ receptor antagonist) or sulpiride (50?mg/kg, i.p., dopamine D₂ receptor antagonist) prevented the antidepressant-like effect of the extract in FST (30?mg/kg). Moreover, ketanserin (5?mg/kg, i.p., preferential 5-HT_2A receptor antagonist) enhanced the effect of the extract in FST.

Discussion and conclusion: The results of the present study indicate that the extract from P. paniculata has an antidepressant-like action that is likely mediated by an interaction with the serotonergic (5-HT_2A receptors), noradrenergic (α₂ and β-receptor) and dopaminergic (D₁ and D₂ receptors) systems.     

Antidepressant-like effects of piperine and its derivative, antiepilepsirine

In the present study, antidepressant-like effects of piperine (PIP) and its derivative, antiepilepsirine (AES), were investigated in two depressive models: forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, the brain monoamine levels and monoamine oxidase A and B (MAO-A and MAO-B) activities were also determined. The research results for the first time indicated that after two weeks of chronic administration, PIP and AES at doses of 10-20 mg/kg significantly reduced the duration of immobility in both FST and TST, without accompanying changes in locomotor activity in the open-field test. But at the dose of 80 mg/kg, the antidepressant activity of both PIP and AES returned to the control level in the TST and FST. In the monoamine assay, chronic AES administration significantly elevated the dopamine level in striatum, hypothalamus and hippocampus, and also increased the serotonin level in the hypothalamus and hippocampus. In contrast, chronic treatment of PIP only enhanced the serotonin level in the hypothalamus and hippocampus but did not influence the dopamine level. Moreover, both PIP and AES showed no effects on level of noradrenaline in these brain regions. The MAO activity assay also indicated that PIP and AES showed a minor MAO inhibitory activity. In the present study, we demonstrated that the antidepressant-like effects of PIP and AES might depend on the augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake. Antidepressant properties of PIP were supposed to be mediated via the regulation of serotonergic system, whereas the mechanisms of antidepressant action of AES might be due to its dual regulation of both serotonergic and dopaminergic systems.     

Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis.     

胡椒碱及其衍生物3,4-次甲二氧桂皮酰哌啶的抗抑郁作用

目的研究胡椒碱及其衍生物3,4次甲二氧桂皮酰哌啶的抗抑郁作用,并对其作用机理进行初步探讨。方法利用小鼠强制游泳实验、悬尾实验等考察胡椒碱和3,4次甲二氧桂皮酰哌啶的抗抑郁作用,并通过测定不同脑区内单胺类神经递质质量浓度以及全脑单胺氧化酶活性变化,探讨作用机制。结果胡椒碱和3,4次甲二氧桂皮酰哌啶(10、20 mg.kg-1)长期给药后,能明显缩短小鼠在行为学实验中的不动状态时间,并且该作用随剂量增大效应逐渐降低,高剂量(80 mg.kg-1)表现出明显的中枢神经抑制作用;能显著提高脑内5羟色胺水平,而对脑内肾上腺素递质水平未见明显影响;具有较弱的单胺氧化酶抑制作用。结论胡椒碱和3,4次甲二氧桂皮酰哌啶具有较好的抗抑郁作用,其作用是通过上调中枢神经系统5羟色胺或多巴胺水平实现的。     

Antidepressant effects of the water extract from Taraxacum officinale leaves and roots in mice

Context: The leaves and roots of the Taraxacum officinale F. (Asteraceae) is widely used as traditional medicinal herb in Eastern Asian countries.

Objective: In the present study, the antidepressant-like effects of the water extract of T. officinale (WETO) leaves and roots were investigated in mice using forced swimming test (FST), tail suspension test (TST) and open field test (OFT).

Materials and methods: Effects of acute (1-day) and chronic treatments (14-days) with WETO (50, 100 and 200?mg/kg) on the behavioral changes in FST, TST and OFT, and the serum corticotrophin releasing factor (CRF), adrenocorticotropic hormone (ACTH) and corticosterone concentration were assessed in mice.

Results: Chronic treatment (14-days) with WETO at the doses of 50, 100 and 200?mg/kg significantly decreased the immobility time in both FST (92.6, 85.1 and 77.4?s) and TST (84.8, 72.1 and 56.9?s). Acute treatment (1-day) with WETO at a dose of 200?mg/kg also markedly decreased the immobility time in both FST (81.7?s) and TST (73.2?s). However, all treatments did not affect the locomotor activity in the OFT. Moreover, FST induced a significant increase in serum CRF (5.8?ng/ml), ACTH (104.7?pg/ml) and corticosterone levels (37.3?ng/ml). Chronic treatment (14-days) with WETO decreased the serum CRF (200?mg/kg: 3.9?ng/ml) and corticosterone (50?mg/kg: 29.9?ng/ml; 100?mg/kg: 22.5?ng/ml; 200?mg/kg: 19.8?ng/ml) levels.

Discussion and conclusion: These results clearly demonstrated the antidepressant effects of WETO in animal models of behavioral despair and suggested the mechanism involved in the neuroendocrine system.     

Depression-resistant endophenotype in mice overexpressing cannabinoid CB2 receptors

Background and purpose:

The present study evaluated the role of CB₂ receptors in the regulation of depressive-like behaviours. Transgenic mice overexpressing the CB₂ receptor (CB2xP) were challenged with different types of acute and chronic experimental paradigms to evaluate their response in terms of depressive-like behaviours.

Experimental approach:

Tail suspension test (TST), novelty-suppressed feeding test (NSFT) and unpredictable chronic mild stress tests (CMS) were carried out in CB2xP mice. Furthermore, acute and chronic antidepressant-like effects of the CB₂ receptor-antagonist AM630 were evaluated by means of the forced swimming test (FST) and CMS, respectively, in wild-type (WT) and CB2xP mice. CB₂ gene expression, brain-derived neurotrophic factor (BDNF) gene and protein expressions were studied in mice exposed to CMS by real-time PCR and immunohistochemistry, respectively.

Key results:

Overexpression of CB₂ receptors resulted in decreased depressive-like behaviours in the TST and NSFT. CMS failed to alter the TST and sucrose consumption in CB2xP mice. In addition, no changes in BDNF gene and protein expression were observed in stressed CB2xP mice. Interestingly, acute administration of AM630 (1 and 3 mg·kg⁻¹, i.p.) exerted antidepressant-like effects on the FST in WT, but not in CB2xP mice. Chronic administration of AM630 for 4 weeks (1 mg·kg⁻¹; twice daily, i.p.) blocked the effects of CMS on TST, sucrose intake, CB₂ receptor gene, BDNF gene and protein expression in WT mice.

Conclusion and implications:

Taken together, these results suggest that increased CB₂ receptor expression significantly reduced depressive-related behaviours and that the CB₂ receptor could be a new potential therapeutic target for depressive-related disorders.     

The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice

Rationale

Evidence suggests that neuronal nicotinic acetylcholine receptor (nAChR) ligand lobeline has antidepressant-like properties.

Objectives

The present study investigated the effects of lobeline on nicotine withdrawal-induced depression-like behavior.

Methods

Adult C57BL/6J mice were exposed to nicotine (200 μg/ml) in drinking solution for 3 weeks. During withdrawal, depression-like behavior was measured by the forced swim test (FST). We also determined norepinephrine (NE) levels in the prefrontal cortex (PFC) and hippocampus during nicotine withdrawal. Furthermore, we determined the effects of repeated treatment with lobeline or a selective α4β2 nAChR ligand 3-(pyridine-3?-yl)-cytisine on brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive element binding (p-CREB) protein expression in the hippocampus.

Results

Withdrawal from chronic nicotine increased immobility time in the FST, a measure for depression-like behavior. Pretreatment with lobeline significantly decreased immobility time during nicotine withdrawal. In addition, pretreatment with lobeline attenuated nicotine withdrawal-induced increased NE levels in the PFC and hippocampus. Further, repeated treatment with lobeline or 3-(pyridine-3?-yl)-cytisine decreased immobility time in the FST and reduced withdrawal-induced increased BDNF and p-CREB expression in the hippocampus.

Conclusions

Taken together, our results indicate that lobeline attenuated nicotine withdrawal-induced depression-like behavior likely by targeting brain nAChRs, noradrenergic neurotransmission, and/or hippocampal BDNF. Thus, lobeline may have some potential to prevent smoking relapse by counteracting nicotine withdrawal-induced depression in humans.     

Acute atorvastatin treatment exerts antidepressant-like effect in mice via the l-arginine–nitric oxide–cyclic guanosine monophosphate pathway and increases BDNF levels

Atorvastatin is a synthetic and lipophilic statin that presents a good effect in decreasing cholesterol levels and is safe and well tolerated. Population-based studies have suggested a positive role of statins in reducing depression risk. This study aimed at investigating the atorvastatin effect in the tail suspension test (TST) and in the forced swimming test (FST). The participation of NMDA receptors and l–arginine–NO–cGMP in an atorvastatin antidepressant-like effect in the TST was evaluated. Acute atorvastatin administration (0.1–30 mg/kg) reduced the immobility time both in TST and FST. A similar effect was observed by using imipramine as a positive control in the TST and FST (1 and 0.1–1 mg/kg, p.o., respectively). An atorvastatin (0.1 mg/kg) antidepressant-like effect was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p.) or sildenafil (5 mg/kg, i.p.). The administration of MK-801 (0.001 mg/kg, i.p.), ketamine (0.1 mg/kg, i.p.), 7-nitroindazole (50 mg/kg, i.p.), methylene blue (20 mg/kg, i.p.), or ODQ (30 pmol/site i.c.v.) in combination with a subeffective dose of atorvastatin (0.01 mg/kg, p.o.) reduced the immobility time in the TST compared to drugs alone, showing the participation of the pathway l-arginine–NO–cGMP. The administration of drugs did not produce any significant alteration in locomotor activity in the open-field test. Acute atorvastatin treatment (0.1–10.0 mg/kg, v.o.) increased the hippocampal BDNF levels, which is an effect that has not been observed in imipramine-treated mice. These results demonstrate that atorvastatin exerts an antidepressant-like effect and point to dependence on the inhibition of NMDA receptors and NO–cGMP synthesis, and on the increase of hippocampal BDNF levels.     

Green tea polyphenols produce antidepressant-like effects in adult mice

Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like effects and the possible mechanism of action of green tea in widely used mouse models of depression. Mice were orally administered green tea polyphenols (GTP; 5, 10 and 20mg/kg) for 7days and assessed in the forced swimming test (FST) and tail suspension test (TST) 60min after the last GTP administration. Serum corticosterone and adrenocorticotrophic hormone (ACTH) levels were also determined immediately after the FST. Green tea polyphenols significantly reduced immobility in both the FST and TST but did not alter locomotor activity in the open field test, suggesting that GTP has antidepressant-like effects, and this action did not induce nonspecific motor changes in mice. Green tea polyphenols also reduced serum corticosterone and ACTH levels in mice exposed to the FST. The present study demonstrated that GTP exerts antidepressant-like effects in a mouse behavioral models of depression, and the mechanism may involve inhibition of the hypothalamic-pituitary-adrenal axis.     

Orthogonal array design for antidepressant compatibility of polysaccharides from Banxia-Houpu decoction,a traditional Chinese herb prescription in the mouse models of depression

The present study investigated antidepressant-like interaction of five herb polysaccharide fractions from Banxia-Houpu decoction, composed of rhizome pinelliae (PRP), magnolia bark (PMB), poria (PPO), ginger rhizome (PGR) and folium perillae (PFP) by a L₁₆(2⁵) orthogonal array design with a two-factor interaction in the tail suspension and forced swimming and tests (TST, FST) in mice. Serotonin (5-HT) and dopamine (DA) levels in whole mouse brain were simultaneously examined after the FST exposure. Polysaccharides PMB, PPO, PFP, and interactions of PRP × PGR, PMB × PFP, PPO × PFP reduced immobility in the mouse FST. Furthermore, PMB and PPO were two principal components of polysaccharides elevating brain 5-HT levels. PFP was an adjuvant component elevating brain DA levels. These results demonstrated that ineffective PRP exhibited antidepressant-like effects when combined with another ineffective PGR, and PFP played a role in assisting effects of PMB and PPO. Therefore, PMB × PFP and PPO × PFP interactions on antidepressant-like effects were the cores in compatibility of polysaccharides from Banxia-Houpu decoction by attenuating abnormalities in the serotonergic and dopaminergic system functions in animal models of depression.     

Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade

Current antidepressants are clinically effective only after several weeks of administration. Ginsenoside Rg3 is one component of ginsenosides, with a similar chemical structure to ginsenoside Rg1. Here, we investigated the antidepressant effects of Rg3 in mouse models of depression. The antidepressant actions of Rg3 were first examined in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and Rg3 treatment were investigated. A tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to determine the pharmacological mechanisms of Rg3. It was found that Rg3 produced antidepressant effects in the FST and TST without affecting locomotor activity. Rg3 also prevented the CSDS-induced depressive-like symptoms. Moreover, Rg3 fully restored the CSDS-induced decrease in the hippocampal BDNF signaling pathway, and use of the BDNF signaling inhibitor blocked the antidepressant effects of Rg3. In conclusion, ginsenoside Rg3 has antidepressant effects via promotion of the hippocampal BDNF signaling pathway.     

The antidepressant-like effects of glutamatergic drugs ketamine and AMPA receptor potentiator LY 451646 are preserved in bdnf⁺/⁻ heterozygous null mice

Accumulating evidence suggests that biogenic amine-based antidepressants act, at least in part, via regulation of brain-derived neurotrophic factor (BDNF) signaling. Biogenic amine-based antidepressants increase BDNF synthesis and activate its signaling pathway through TrkB receptors. Moreover, the antidepressant-like effects of these molecules are abolished in BDNF deficient mice. Glutamate-based drugs, including the NMDA antagonist ketamine, and the AMPA receptor potentiator LY 451646, mimic the effects of antidepressants in preclinical tests with high predictive validity. In humans, a single intravenous dose of ketamine produces an antidepressant effect that is rapid, robust and persistent. In this study, we examined the role of BDNF in expression of the antidepressant-like effects of ketamine and an AMPA receptor potentiator (LY 451646) in the forced swim test (FST). Ketamine and LY 451646 produced antidepressant-like effects in the FST in mice at 45 min after a single injection, but no effects were observed one week after a single ketamine injection. As previously reported, the effects of imipramine in the forced swim test were blunted in heterozygous BDNF knockout (bdnf(+/-)) mice. However ketamine and LY 451646 produced similar antidepressant-like responses in wildtype and bdnf(+/-) mice. Neither ketamine nor LY 451646 significantly influenced the levels BDNF or TrkB phosphorylation in the hippocampus when assessed at 45 min or 7 days after the drug administration. These data demonstrate that under the conditions tested, neither ketamine nor the AMPA-potentiator LY 451656 activate BDNF signaling, but produce a characteristic antidepressant-like response in heterozygous bdnf(+/-) mice. These data indicate that unlike biogenic amine-based agents, BDNF signaling does not play a pivotal role in the antidepressant effects of glutamate-based compounds. This article is part of a Special Issue entitled 'Anxiety and Depression'.     

The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice

Rationale Increases in cholinergic transmission are linked to depression in human subjects and animal models. We therefore examined the effect of decreasing nicotinic acetylcholine receptor (nAChR) activity in tests of antidepressant efficacy using C57BL/6J mice.Objectives We determined whether the noncompetitive nAChR antagonist mecamylamine had antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). These experiments were repeated in mice lacking either the β2- or α7-nAChR subunits to identify the nAChR subunits involved in mediating the antidepressant response to mecamylamine.Materials and methods Adult mice on the C57BL/6J background were acutely administered mecamylamine i.p. 30 min before testing in the FST or TST.Results A dose–response study showed that mecamylamine significantly decreased immobility time in the TST at the 1.0-mg/kg dose but did not alter baseline locomotor activity. The competitive nAChR antagonist dihydro-β-erythroidine, but not the blood–brain barrier impermeant antagonist hexamethonium, also decreased immobility in the TST. One milligram per kilogram of mecamylamine also significantly decreased time immobile in the FST whereas both β2- and α7-knockout mice were insensitive to the effects of mecamylamine in the FST.Conclusions Decreased activity of central nAChRs has antidepressant-like effects in both the TST and FST and these effects are dependent on both β2 and α7 subunits. Therefore, compounds that decrease nAChR activity may be attractive new candidates for development as antidepressants in humans.