scholarly journals Discovery of 1,3-diyne compounds as novel and potent antidepressant agents: synthesis, cell-based assay and behavioral studies

RSC Advances ◽  
2017 ◽  
Vol 7 (26) ◽  
pp. 16005-16014 ◽  
Author(s):  
Kai-Qing Ma ◽  
Yan-Hong Miao ◽  
Xiao Li ◽  
Yu-Zhi Zhou ◽  
Xiao-Xia Gao ◽  
...  

1,3-Diynes compound 7a protected the corticosterone-injured PC12 cells through regulation of the apoptosis related proteins and exerted antidepressant effect in mice forced swim test in a concentration-dependent manner.

2020 ◽  
Author(s):  
Jinqiang Zhang ◽  
Saini Yi ◽  
Yahui Li ◽  
Chenghong Xiao ◽  
Chan Liu ◽  
...  

AbstractAimIndoleamine 2, 3-dioxygenase (IDO) is responsible for the progression of the kynurenine pathway, which has been implicated in the pathophysiology of inflammation-induced depression. It has been reported that asperosaponin VI (ASA VI) could play a neuroprotective role through anti-inflammatory and antioxidant. In this study, we examined the antidepressant effect of ASA VI in LPS-treated mice and further explored its molecular mechanism by insight into the microglial kynurenine pathway.MethodsTo produce the model, lipopolysaccharide (LPS) (0.83 mg/kg) was administered intraperitoneally to mice. The mice received ASA VI (10 mg/kg, 20mg/kg, 40mg/kg and 80mg/kg, i.p.) thirty minutes prior to LPS injection. Depressive-like behaviors were evaluated based on the duration of immobility in the forced swim test. Microglial activation and inflammatory cytokines were detected by immunohistochemistry, real-time PCR and ELISA. The TLR4/NF-ĸB signaling pathway and the expression of IDO, GluA2, and CamKIIβ were measured by western blotting.ResultsASA VI demonstrated significant antidepressant activity in the presence of LPS on immobility and latency times in the forced swim test. The LPS-induced activation of microglia and inflammatory response were inhabited by ASA VI in a dose-dependent manner. TLR4/NF-κB signaling pathway also was suppressed by ASA VI in the hippocampus and prefrontal cortex of LPS-treated mice. Furthermore, ASA VI inhibited the increase in IDO protein expression and normalized the aberrant glutamate transmission in the hippocampus and prefrontal cortex as a result of LPS administration.ConclusionOur results propose a promising antidepressant effect for ASA VI possibly through the downregulation of IDO expression and normalization of the aberrant glutamate transmission. This remedying effect of ASA VI could be attributed to suppress microglia-mediated neuroinflammatory response via inhibiting the TLR4/NF-κB signaling pathway.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ridge G. Weston ◽  
Paul J. Fitzgerald ◽  
Brendon O. Watson

The anesthetic drug ketamine has been successfully repurposed as an antidepressant in human subjects. This represents a breakthrough for clinical psychopharmacology, because unlike monoaminergic antidepressants, ketamine has rapid onset, including in Major Depressive Disorder (MDD) that is resistant to conventional pharmacotherapy. This rapid therapeutic onset suggests a unique mechanism of action, which continues to be investigated in reverse translational studies in rodents. A large fraction of rodent and human studies of ketamine have focused on the effects of only a single administration of ketamine, which presents a problem because MDD is typically a persistent illness that may require ongoing treatment with this drug to prevent relapse. Here we review behavioral studies in rodents that used repeated dosing of ketamine in the forced swim test (FST), with an eye toward eventual mechanistic studies. A subset of these studies carried out additional experiments with only a single injection of ketamine for comparison, and several studies used chronic psychosocial stress, where stress is a known causative factor in some cases of MDD. We find that repeated ketamine can in some cases paradoxically produce increases in immobility in the FST, especially at high doses such as 50 or 100 mg/kg. Several studies however provide evidence that repeated dosing is more effective than a single dose at decreasing immobility, including behavioral effects that last longer. Collectively, this growing literature suggests that repeated dosing of ketamine has prominent depression-related effects in rodents, and further investigation may help optimize the use of this drug in humans experiencing MDD.


Author(s):  
Chiranjeevi Bonda ◽  
Sudhir Pawar ◽  
Jaisen Lokhande

Background: The aim of the study was to evaluate the antidepressant effect of opioid analgesic tramadol using forced swim test and tail suspension test models.Methods: The antidepressant effect was assessed by recording the immobility time in Forced swim test (FST) and Tail suspension test (TST). The mice were randomly divided into five groups. Mice belonging to group I was given normal saline (0.1ml/kg) which acted as control. Group II received imipramine (15mg/kg) considered as the standard drug tramadol was given in graded dose (10, 20 and 40 mg/kg) to mice of groups III, IV, V respectively. All drugs were administered intraperitoneally for seven successive days; test was done on 7th day.Results: Tramadol and Imipramine showed antidepressant activity when compared to control. There is dose dependent increase in antidepressant activity of tramadol. The antidepressant activity of imipramine was significantly (P<0.05) more than tramadol at dose 10 and 20 mg/kg but antidepressant activity with tramadol 40mg/kg was comparable to imipramine treated mice.Conclusions: The results of this study indicated the presence of antidepressant activity of tramadol at 40mg/kg.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Pravin O. Patil ◽  
Sanjay B. Bari

The present study refers to the synthesis of new antidepressant candidates using the indole scaffold. In an attempt to identify potential lead antidepressant agents, a number of indole molecules, incorporating isoxazoline, were synthesized by microwave-assisted synthesis. The antidepressant activity of the synthesized compounds(3a–3n)was evaluated by forced swim test in mice and their locomotor activity was assessed using actophotometry. The present paper showed significant antidepressant activity for all compounds of the series and no significant change in locomotor activity of mice. Compounds3dand3jwere found to be potent molecules of this series, when compared with the reference drugs imipramine and fluoxetine. It clearly demonstrated that replacement of aromatic core by appropriate heterocycles such as pyridine and pyrrole on the 5-(1H-Indol-3-yl)-3-(Phenyl)-4,5-dihydroisoxazoline(3a)would generate more potent derivatives. Thus, these compounds can serve as potential leads for further antidepressant studies.


2011 ◽  
Vol 26 (S2) ◽  
pp. 802-802
Author(s):  
N. Kokras ◽  
C. Dalla ◽  
K. Antoniou ◽  
Z. Papadopoulou-Daifoti

IntroductionSex differences have been described in depression and more recently in antidepressant response. Animal models and in particular the Forced Swim Test (FST), are widely used to investigate the behavioural response to stress and to antidepressant treatment.ObjectivesThe present study explored sex differences in the stress response during the FST and examined whether antidepressant treatment alleviates the sex-differentiated stress response.MethodsAdult male and female Wistar rats were subjected to a 15 min FST session and then treated with three injections of sertraline 10 mg/kg or vehicle at 0, 19 and 23 hours post-FST. Twenty-four hours after the first FST, they had a second 5 min FST session and their behaviour was recorded.ResultsVehicle-treated females exhibited 66% longer duration and 70% shorter latency of immobility than males, suggesting enhanced levels of despair. Sertraline did not significantly affect immobility, but exerted its antidepressant effect by elongating swimming duration in both sexes and shortening climbing behaviour in males only. In contrast, to vehicle-treated rats, no sex differences were observed in sertraline-treated rats in any of these behavioural parameters. However, sex-differences in head swinging behaviour, which is unaffected by sertraline treatment, were still observed in sertraline-treated rats.ConclusionsFemales appear more vulnerable than males to the FST, but the post-treatment organisation of FST behaviour is not sex-differentiated. Antidepressants seem to modulate the behavioural response in FST in a sex-specific way, due to sex differences in baseline FST performance. Consequently, the sex-differentiated stress response profile during FST is attenuated by antidepressant treatment.


2016 ◽  
Vol 11 (3) ◽  
pp. 711 ◽  
Author(s):  
Zahra Rabiei ◽  
Mostafa Gholami ◽  
Mahmoud Rafieian-Kopaei

<p class="Abstract">The aim of this study is to investigate the antidepressant effects of <em>Mentha pulegium</em> essential oil in BALB/c mice. Six experimental groups (7 mice each) were used. Forced swim test was performed 30 min after essential oil injection. In the groups receiving <em>M. pulegium</em> essential oil (50, 75 and 100 mg/kg), immobility duration significantly decreased compared to the control group. <em>M. pulegium</em> (50 and 75 mg/kg) resulted in significant decrease in nitrate/nitrite content in serum compared to the control group. <em>M. pulegium</em> essential oil antidepressant effect that may be due to the inhibition of oxidative stress.  The results showed that decrease in nitrate/nitrite content in serum and high anti-oxidant effects of M. pulegium essential oil.</p><p><strong>Video clip:</strong></p><p><a href="https://youtube.com/v/qfmjCf5FNMk">Immobility in Forced Swim Test</a>: 13 sec</p><p><a href="https://youtube.com/v/oqWS13JzQtQ">Mobility in Forced Swim Test</a>: 19 sec</p><p> </p><p> </p>


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