scholarly journals Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Chun Yang ◽  
Wen-Yuan Li ◽  
Hai-Yin Yu ◽  
Zhi-Qin Gao ◽  
Xiang-Liu Liu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mammalian Target Of Rapamycin ◽  
Antidepressant Activity ◽  
Rat Hippocampus ◽  
Target Of Rapamycin ◽  
Acute Administration ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Swimming Test ◽  
Fast Acting

Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR) in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST). Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex

2014 ◽  
Vol 29 (7) ◽  
pp. 419-423 ◽  
Author(s):  
W. Zhou ◽  
N. Wang ◽  
C. Yang ◽  
X.-M. Li ◽  
Z.-Q. Zhou ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Mammalian Target Of Rapamycin ◽  
Rat Hippocampus ◽  
Bdnf Expression ◽  
Prefrontal Cortical ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Underlying Mechanisms

AbstractKetamine exerts fast acting, robust, and lasting antidepressant effects in a sub-anesthetic dose, however, the underlying mechanisms are still not fully elucidated. Recent studies have suggested that ketamine's antidepressant effects are probably attributed to the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The present study aimed to observe the effects of AMPA receptor modulators on mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF) expression during the procedure of ketamine exerting antidepressant effects. Therefore, we pretreated rats with NBQX, an AMPA receptor antagonist, or CX546, an AMPA receptor agonist, and subsequently observed the immobility time during the forced swimming test (FST) and the hippocampal and prefrontal cortical levels of mTOR and BDNF. The results showed ketamine decreased the immobility time of rats during the FST and increased the hippocampal and prefrontal cortical mTOR and BDNF. NBQX pretreatment significantly increased the immobility time and decreased the levels of mTOR and BDNF when compared with vehicle 1 (DMSO) pretreatment. CX546 pretreatment significantly decreased the immobility time and increased the levels of mTOR and BDNF when compared with vehicle 2 (DMSO + ethanol) pretreatment. Our results suggest ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of mTOR and BDNF in rat hippocampus and prefrontal cortex.

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

2019 ◽  
Vol 16 (4) ◽  
Author(s):  
Azadeh Mesripour ◽  
Neda Rabian ◽  
Afsaneh Yegdaneh
Keyword(s):  
Single Dose ◽  
Biological Activities ◽  
Food Resource ◽  
Control Group ◽  
Mice Model ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Term Administration ◽  
Swimming Test

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

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

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Azadeh Mesripour ◽  
Shahrzad Shahnooshi ◽  
Valiollah Hajhashemi
Keyword(s):  
Side Effects ◽  
Forced Swimming Test ◽  
Interferon Alfa ◽  
Interferon Α ◽  
High Dose ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Inflammatory Drugs ◽  
Swimming Test ◽  
Psychiatric Side Effects

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

scholarly journals Identifying the active components of Baihe–Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ming Zhong ◽  
Xiaoting Tian ◽  
Shuoji Chen ◽  
Mingcang Chen ◽  
Ziqiong Guo ◽  
...  
Keyword(s):  
Oral Administration ◽  
Tail Suspension Test ◽  
Active Components ◽  
Evaluation Standards ◽  
Hepatic Disposition ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Quantitative Analyses ◽  
Swimming Test ◽  
The Brain

Abstract Background Modern pharmacological studies have demonstrated that Baihe–Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds. Methods In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing. Results Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression. Conclusions This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.

Ketamine Exhibits Different Neuroanatomical Profile After Mammalian Target of Rapamycin Inhibition in the Prefrontal Cortex: the Role of Inflammation and Oxidative Stress

2016 ◽  
Vol 54 (7) ◽  
pp. 5335-5346 ◽  
Author(s):  
Helena M. Abelaira ◽  
Gislaine Z. Réus ◽  
Zuleide M. Ignácio ◽  
Maria Augusta B. dos Santos ◽  
Airam B. de Moura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prefrontal Cortex ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
And Oxidative Stress

scholarly journals Evaluation of Antidepressant Activity of Ethanolic Extract of Abies webbiana and Berberis aristata in Laboratory Animals

2019 ◽  
Vol 9 (1) ◽  
pp. 244-247 ◽  
Author(s):  
Sucheta Gautam ◽  
Neetu Sachan ◽  
Alankar Shrivastav ◽  
Dilipkumar Pal
Keyword(s):  
Ethanolic Extract ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Laboratory Animals ◽  
Control Group ◽  
Standard Group ◽  
Therapeutic Effects ◽  
Conventional Drug ◽  
Immobility Time ◽  
Swimming Test

Abstract Objective: Abies webbiana and Berberis aristata is an herbal plant that has several therapeutic effects. It also heals depression, grief, nervous stress and tension. In the present study we evaluated anti-depressant effect of ethanolic extract from Abies webbiana and Berberis aristata by using Forced Swimming Test (FST) and Tail Suspension Test (TST). Methods: Two doses of ethanolic extract of Abies webbiana and berberis aristata (200 mg/kg and 400 mg/kg) was given orally. Immobility time were measured after 30 min after the dosing and compared with control group and Flouxetine (25mg/kg) as a standard group. Results: The ethanolic extract of BA and AW (400 mg/kg) was found to be effective and it exhibited activity similar to that of the conventional drug Flouxetine (25mg/kg) (p<0.001) whereas 200 mg/kg dose showed higher activity with significantly increased swimming time and suspension time and decreased immobility time than 400 mg/kg of ethanolic extracts and Flouxetine (25mg/kg). Conclusion: These results proposed 400 mg/kg of ethanolic extract was showed higher anti-depressant activity as compared to control which is similar to the standard.

Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus

2008 ◽  
Vol 32 (1) ◽  
pp. 140-144 ◽  
Author(s):  
Lêda S.B. Garcia ◽  
Clarissa M. Comim ◽  
Samira S. Valvassori ◽  
Gislaine Z. Réus ◽  
Luciana M. Barbosa ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Forced Swimming ◽  
Rat Hippocampus ◽  
Acute Administration ◽  
Swimming Test

scholarly journals mTOR Knockdown in the Infralimbic Cortex Evokes A Depressive-Like State in Mouse

2021 ◽  
Vol 22 (16) ◽  
pp. 8671
Author(s):  
Emilio Garro-Martínez ◽  
Maria Neus Fullana ◽  
Eva Florensa-Zanuy ◽  
Julia Senserrich ◽  
Verónica Paz ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Tail Suspension Test ◽  
Mtor Signaling ◽  
Small Interfering Rnas ◽  
Mtor Signaling Pathway ◽  
Bdnf Expression ◽  
Protein Levels ◽  
Antidepressant Effects ◽  
Post Infusion ◽  
Swimming Test

Fast and sustained antidepressant effects of ketamine identified the mammalian target of rapamycin (mTOR) signaling pathway as the main modulator of its antidepressive effects. Thus, mTOR signaling has become integral for the preclinical evaluation of novel compounds to treat depression. However, causality between mTOR and depression has yet to be determined. To address this, we knocked down mTOR expression in mice using an acute intracerebral infusion of small interfering RNAs (siRNA) in the infralimbic (IL) or prelimbic (PrL) cortices of the medial prefrontal cortex (mPFC), and evaluated depressive- and anxious-like behaviors. mTOR knockdown in IL, but not PrL, cortex produced a robust depressive-like phenotype in mice, as assessed in the forced swimming test (FST) and the tail suspension test (TST). This phenotype was associated with significant reductions of mTOR mRNA and protein levels 48 h post-infusion. In parallel, decreased brain-derived neurotrophic factor (BDNF) expression was found bilaterally in both IL and PrL cortices along with a dysregulation of serotonin (5-HT) and glutamate (Glu) release in the dorsal raphe nucleus (DRN). Overall, our results demonstrate causality between mTOR expression in the IL cortex and depressive-like behaviors, but not in anxiety.

scholarly journals Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yujin Choi ◽  
Yunna Kim ◽  
Hwa-Young Lee ◽  
Seung-Hun Cho
Keyword(s):  
Prefrontal Cortex ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Antidepressant Agent ◽  
Immobility Time ◽  
Swimming Test ◽  
Asian Pacific ◽  
Sucrose Preference Test ◽  
Tetragonia Tetragonioides

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test

2018 ◽  
Vol 32 (8) ◽  
pp. 922-931 ◽  
Author(s):  
Ariandra G Sartim ◽  
Amanda J Sales ◽  
Francisco S Guimarães ◽  
Sâmia RL Joca
Keyword(s):  
Dorsal Hippocampus ◽  
Forced Swim Test ◽  
Mammalian Target Of Rapamycin ◽  
Antidepressant Drugs ◽  
Brain Regions ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Swim Test ◽  
Forced Swim ◽  
Immobility Time

Background: Cannabidiol is a non-psychotomimetic compound with antidepressant-like effects. However, the mechanisms and brain regions involved in cannabidiol effects are not yet completely understood. Brain-derived neurotrophic factor/tropomyosin-receptor kinase B/mammalian target of rapamycin (BDNF-TrkB-mTOR) signaling, especially in limbic structures, seems to play a central role in mediating the effects of antidepressant drugs. Aim: Since it is not yet known if BDNF-TrkB-mTOR signaling in the hippocampus is critical to the antidepressant-like effects of cannabidiol, we investigated the effects produced by cannabidiol (10/30/60 nmol/0.2 µL) micro-injection into the hippocampus of mice submitted to the forced swim test and to the open field test. Methods: Independent groups received intra-hippocampal injections of rapamycin (mTOR inhibitor, 0.2 nmol/0.2 µL) or K252 (Trk antagonist, 0.01 nmol/0.2 µL), before the systemic (10 mg/kg) or hippocampal (10 nmol/0.2µL) injection of cannabidiol, and were submitted to the same tests. BDNF levels were analyzed in the hippocampus of animals treated with cannabidiol (10 mg/kg). Results: Systemic cannabidiol administration induced antidepressant-like effects and increased BDNF levels in the dorsal hippocampus. Rapamycin, but not K252a, injection into the dorsal hippocampus prevented the antidepressant-like effect induced by systemic cannabidiol treatment (10 mg/kg). Differently, hippocampal administration of cannabidiol (10 nmol/0.2 µL) reduced immobility time, an effect that was blocked by both rapamycin and K252a local microinjection. Conclusion: Altogether, our data suggest that the hippocampal BDNF-TrkB-mTOR pathway is vital for cannabidiol-induced antidepressant-like effect when the drug is locally administered. However, other brain regions may also be involved in cannabidiol-induced antidepressant effect upon systemic administration.

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