scholarly journals Adenylyl Cyclase (AC) Mediates the Antidepressant-Like Effects of Tropisetron on a Mouse Model of Maternal Separation Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Ali Hosseinzadeh ◽  
Shakiba Nasiri Boroujeni ◽  
Elham Saghaei ◽  
Zahra Loriooini ◽  
Saeid Habibian Dehkordi ◽  
...  

The adenylyl cyclase (AC) pathway is involved in the pathophysiology of depression. Finding new antidepressants with high medicinal properties and low side effects is warranted. Therefore, this study was designed to determine the antidepressant-like effect of tropisetron on a maternal separation (MS) model in mice, considering the possible role of AC. NMRI male mice were divided into eleven groups. The control group was treated with saline and MS groups were treated with saline, tropisetron (a 5-HT3 receptor antagonist) at doses of 1, 3, and 5 mg/kg; forskolin (an activator of AC) at doses of 5, 10, and 25 mg/kg; a subeffective dose of forskolin with a subeffective dose of tropisetron; and an effective dose of tropisetron plus an effective dose of NB001 (3 mg/kg) (an AC inhibitor). After treatment, animals were subjected to behavioral tests including the forced swimming test (FST), splash test, and open field test (OFT). We showed that MS caused depressive-like behaviors determined as an increase in the immobility time in the forced swimming test (FST) and decreased grooming time in the splash test. Our results showed that administration of tropisetron, as well as forskolin, mitigated the depressive-like behaviors in MS mice. We found that coadministration of a subeffective dose of tropisetron plus a subeffective dose of forskolin potentiated the antidepressant-like effect of tropisetron. However, coadministration of an effective dose of NB001 with an effective dose of tropisetron did not significantly affect the antidepressant-like effect of tropisetron. We concluded that the antidepressant-like effects of tropisetron on MS mice are partially mediated through the adenylyl cyclase pathway.

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1 ◽  
Author(s):  
A. Kikko ◽  
P. Koerich ◽  
E. Bondan ◽  
F. Nunes ◽  
M. Pizzolatti ◽  
...  

The aim of the present work was to investigate if flowers extract (FE) and leaf extract (LE) of Baccharis ilimita (Asteraceae) induced antidepressant-like effect. Previous phytochemical investigations have shown the presence of structurally and biogenetically diverse secondary metabolites in this gene, such as flavonoids, diterpenes and triterpenes. Male Swiss mice were injected with FE and LE (12.5; 25.0 or 50.0 mg/kg; i.p.) or saline (S) and after 30 min, they were tested in the forced swimming test (FST). The results showed that FE and LE (50 mg/kg) decreased the duration of immobility time in comparison to the control group (S: 114.8s ± 10.23; FE50: 47.52s ± 9.45; LE50: 53.36s ± 10.38). However, the 12.5 and 25.0 mg/kg doses had no effect on the immobility time in comparison to the control group. The FE and LE did not produce any change in ambulation in mice when tested in an open field. The imipramine (IMP; 15.0 mg/kg i.p.) was used as the positive control. Our results suggested that FE and LE of Baccharis ilimita presents antidepressant-like effect in mice. Such results suggest that the antidepressant-like effect may be attributed at lest partially the flavonoids or the interaction of the active(s) principle(s) present in this plant.Descritores:Baccharis ilimita. Forced swimming test. Depression. Mice.


2020 ◽  
Author(s):  
Ruoyi Liu ◽  
Li Xu ◽  
Shujun Zhang ◽  
Yue Wang ◽  
Peng Zhao

Abstract Objective: To explore the efficacy and possible mechanism of Danzhi Xiaoyao Powder in the treatment of scratching behavior worsened by psychological factors. Methods: Male BALB/c mice were divided into control group (CON group), chronic WAS group(WAS group) and chronic WAS + Danzhi Xiaoyao Powder group(DZX group). All mice excluded control group were exposed to 1 h water avoidance stress (WAS) for ten consecutive days. DZX group were given Danzhi Xiaoyao Powder solution by intragastric administration every day, and the other two groups were given the same amount of saline. Twenty-four hours after the last stress session, the mice were injected into the back of the neck with a condensation product of N-methyl-p- methoxyphenethylamine with formaldehyde (compound 48/80), and their scratching behavior was then observed for 120 min. The scratching number was recorded, th histamine levels in the plasma were examined, and the behavioral changes of depression in mice before and after treatment were observed by open field test and forced swimming test. Results: The scratching number was significantly higher in the WAS group than in the DZX group, which still higher than in the CON group. The peak histamine in the plasma after the compound 48/80 injection were also significantly higher in the WAS group in comparison to the DZX group. In terms of depression behavior, the number of standing in the DZX group was more than that in the WAS group and less than that in the CON group, and the immobility time in the forced swimming test was less than that in the WAS group and more than that in the CON group. Conclusion: Danzhi Xiaoyao Powder can relieve the scratching behavior of mice under the influence of WAS, and its possible mechanism is to control the release of histamine and improve the depressive state of mice.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zahra Lorigooini ◽  
Shakiba Nasiri Boroujeni ◽  
Mohammad Sayyadi-Shahraki ◽  
Mohammad Rahimi-Madiseh ◽  
Elham Bijad ◽  
...  

Background and Aim. Depression is a social problem with high economic burden in the society. Finding an effective agent with high efficacy and few side effects is therefore needed. Involvement of neuroimmune response as well as nitric oxide (NO) has been determined in the pathophysiology of depression. Limonene is a terpene with various pharmacological properties. Thus, we aimed to evaluate antidepressant-like effect of limonene on a mouse model of maternal separation (MS) focusing on neuroinflammation and NO level in the hippocampus. Methods. Mice were randomly divided into experimental groups as follows: the control group received normal saline and MS groups received normal saline, limonene (10 and 20 mg/kg), L-NAME (10 mg/kg), L-arginine (L-arg) (75 mg/kg), limonene (10 mg/kg) plus L-NAME, and limonene (20 mg/kg) plus L-arg. Behavioral tests including the forced swimming test (FST), open field test (OFT), and splash test were performed. Finally, serum and hippocampal nitrite levels as well as the expression of inflammatory genes (IL-1β and TNF-α) in the hippocampus were measured. Results. We showed that MS caused depressive-like behavior. Treatment of MS mice with limonene reduced the duration of immobility time in FST and increases the grooming activity time in the splash test. Limonene also reduces serum and brain nitrite levels and reduces the expression of IL-1β and TNF-α in the hippocampus. We found that L-NAME potentiated the effects of a subeffective dose of limonene. Conclusion. We concluded that the antidepressant-like effects of limonene are probably mediated through inhibition of neuroinflammation and attenuation of nitrite levels in the hippocampus.


2008 ◽  
Vol 594 (1-3) ◽  
pp. 117-124 ◽  
Author(s):  
Sara Guzzetti ◽  
Eleonora Calcagno ◽  
Alessandro Canetta ◽  
Giuseppina Sacchetti ◽  
Claudia Fracasso ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Anjomshoa ◽  
Shakiba Nasiri Boroujeni ◽  
Sorayya Ghasemi ◽  
Zahra Lorigooini ◽  
Ahmad Amiri ◽  
...  

Background and Aim. Rutin is a flavonol with neuroprotective activity. The aim of the present study is to investigate the role of the glutamatergic system in the antidepressant-like effect of rutin in a mouse model of maternal separation (MS) stress focusing on histological changes in the CA3 area of the hippocampus. Methods. Mouse neonates were exposed to MS paradigm 3 hours daily from postnatal days (PND) 2 to 14. The control and MS mice were divided separately into 16 groups (n=8) (8 groups for each set) including mice that received normal saline, mice that received rutin at doses of 10, 50, and 100 mg/kg, mice that received NMDA at a dose of 150 mg/kg, mice that received ketamine (NMDA antagonist) at a dose of 0.25 mg/kg, mice that received NMDA antagonist plus a subeffective dose of rutin, and mice that received NMDA plus an effective dose of rutin. Forced swimming test (FST) was performed. Afterwards, the hippocampus was evaluated in cases of histopathological changes as well as expression of NR2A and NR2B genes. Results. Rutin significantly reduced immobility time in the FST. The expression of NR2A and NR2B subunits of NMDA receptor in MS mice was significantly higher than that in the control group. Rutin significantly decreased the expression of NR2B and NR2A subunits in the hippocampus. The CA3 diameter and percentage of dark neurons in the hippocampus of MS mice significantly decreased and increased, respectively, which partially reversed following rutin administration. Conclusion. Rutin, partially, through a neuroprotective effect on the hippocampus exerted antidepressant-like effect. We concluded that NMDA receptors, at least in part, mediated the beneficial effect of rutin.


1991 ◽  
Vol 105 (4) ◽  
pp. 525-529 ◽  
Author(s):  
Ella M. Nikulina ◽  
Julia A. Skrinskaya ◽  
Nina K. Popova

Author(s):  
Hossein Omidi-Ardali ◽  
Abolfazl Ghasemi Badi ◽  
Elham Saghaei ◽  
Hossein Amini-Khoei

AbstractObjectivesPrevious studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).MethodsThe antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.ResultsFindings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.ConclusionsOur findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.


2011 ◽  
Vol 224 (2) ◽  
pp. 336-343 ◽  
Author(s):  
Mohammad Salehi Sadaghiani ◽  
Mehrak Javadi-Paydar ◽  
Mohammad Hadi Gharedaghi ◽  
Yashar Yousefzadeh Fard ◽  
Ahmad Reza Dehpour

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