scholarly journals Limonene through Attenuation of Neuroinflammation and Nitrite Level Exerts Antidepressant-Like Effect on Mouse Model of Maternal Separation Stress

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.

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.


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.


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.


2021 ◽  
Vol 10 (11) ◽  
pp. e191101119571
Author(s):  
Amanda Fonseca Costa Assunção ◽  
Nícolas Davidson Sérvulo Rodrigues ◽  
Andreia Viana da Costa Sampaio ◽  
Karolinny dos Santos Silva ◽  
Laryssa Roque da Silva ◽  
...  

Objective: To evaluate the possible antidepressant effects of alpha-terpineol in rodents. Material and Methods: Depression levels were analyzed by comparing the total immobility time presented by the animals of the experimental groups in the test session, using the Forced Swimming Test and the Tail Suspension Test. The parameters of locomotion (central, peripheral and total) and motor coordination were evaluated in the Open Field Test and in the Rota Rod Test, respectively. In the second stage, the involvement of the noradrenergic system in the antidepressant action of alpha-terpineol in Forced Swimming Test was investigated. Results and Discussion: After performing the experimental tests, it was observed that the animals that received alpha-terpineol had reduced immobility time in Forced Swimming Test and Tail Suspension Test, compared to the other groups. In the Open Field Test and Rota-rod, the mice showed, respectively, good exploratory activity and motor coordination during the tests. In addition, the study of the Noradrenergic System proved to be a promising mechanism used during its antidepressant action. Conclusion: In view of the results of the experimental tests, alpha-terpineol presented similar responses to those found in other monoterpenes investigated in the literature. Thus, it is shown as a promising antidepressant to be used clinically in humans, with less side effects and low production cost.


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.


2021 ◽  
Author(s):  
Minghui Tang ◽  
Yong Ai ◽  
Siyang Zhu ◽  
Ni Song ◽  
Xian Xu ◽  
...  

Abstract Citrus reticulata, has been used for various diseases such as cough. According to previous studies, the essential oil of C. reticulata (CREOs) have been shown to be effectively alleviate depression-like behaviors in mice. This study is aimed to investigate the antidepressant-like effect of CREOs in the rapid reserpine-induced depression model mice as well as its possible mechanisms. The experiment was conducted in six groups, each with four mice. The essential oil group and the control group were administered by sniffing (1h/d), while the reserpine group and fluoxetine group by intraperitoneal injection. Body weight, forced swimming test (FST) and tail suspension test (TST) were used to assess depressive behavior. The compositions and contents of CREOs were analyzed by GC-MS. The results indicated that reserpine could reduce the weight of mice and prolong the immobility time of FST and TST. Moreover, the level of 5HT-1A, GR and Nissl bodies in the brain tissue were significantly reduced, while the level of BDNF was increased in reserpine-treated mice. The administration of CREOs could effectively inhibit the weight loss and the prolongation of immobility time caused by reserpine. In addition, the treatment of CREOs has also been shown to reverse the changes in Nissl body, 5-HT, GR and BDNF levels. Limonene was the main active component of CREOs and might be related to the reduction of BDNF. By up-regulating the level of BDNF, CREOs could regulate the hyperexcitability of the HPA axis, thereby increasing the level of neurotransmitters and restoring neurons.


Author(s):  
Mehmet Hanifi Tanyeri ◽  
Mehmet Emin Buyukokuroglu ◽  
Pelin Tanyeri ◽  
Rumeysa Keles Kaya ◽  
Aykut Ozturk ◽  
...  

Aims: Benign prostatic hyperplasia (BPH) is common urological disease, is characterized by lower urinary tract syndrome, usually associated with sexual dysfunctions. The aim of present study is to investigate the effects of terazosin, silodosin and alfuzosin which are the main treatment options for BPH on depression and anxiety to understand whether these drugs may be effective in BPH caused mood disorders. Study Design: All the drugs were given intraperitoneally (i.p.) in a volume of 0.1 ml per 10 g body weight of mice. Drugs were given 30 min before the experiment. We investigated the effects of terazosin, silodosin and alfuzosin on depression and anxiety, in mice. Place and Duration of Study: Sample: Department of Pharmacology and Department of Urology, Sakarya University, Animal Research Center, between June 2019 and September 2020. Methodology: Here, we examined the effects of terazosin (0.5, 1, 2 mg/kg), silodosin silodosin (1, 3, 10 mg/kg) and alfuzosin (3, 6 and 9 mg/kg) on depression and anxiety by using forced swimming test and elevated plus maze test, respectively, in mice (n:96). Additionally, the locomotor activity was evaluated by open field test. Results: All doses of terazosin, alfuzosin and silodosin significantly increased immobility time, compared to saline group. Silodosin and alfuzosin prolonged the time spent in open arms but terazosin decreased the time spent in open arms compared to saline group. Terazosin, silodosin (1 and 3 mg/kg) and alfuzosin (3 and 6 mg/kg) did not have any effect on the number of entries into the open arms while silodosin (10 mg/kg) and alfuzosin (9 mg/kg) increased the number of entries into open arms. Conclusion: We found that silodosin and alfuzosin had antidepressant and anxiolytic-like effects, while terazosin had depressant and anxiogenic effects. Patients with BPH who need antidepressant and anxiolytic treatment can be treated with a single drug instead of multiple medications.


2019 ◽  
Vol 29 (2) ◽  
pp. 113-120
Author(s):  
Maribel Herrera-Ruiz ◽  
Mayra A. Santillán-Urquiza ◽  
Ofelia Romero-Cerecero ◽  
Alejandro Zamilpa ◽  
Enrique Jiménez-Ferrer ◽  
...  

Objective: To evaluate the antidepressant effect of Bauhinia blakeana and a standardized fraction in the forced swimming test (FST) on mice with neuroinflammation induced with lipopolysaccharides (LPS). Materials and Methods: Evaluation of the antidepressant effect of Bauhinia blakeana hydroalcoholic extract (BbHA) and its fractions was carried out in behavioral tests on mice with LPS-induced neuroinflammation. Results: BbHA had a significant antidepressant effect, measured on healthy mice in the FST. Bio-guided chemical separation of the extract produced a methanolic fraction (BbMe), which decreased the immobility time in FST. In this test, the intraperitoneal administration of LPS induced depression in mice, and BbHA and BbMe counteracted this effect, significantly decreasing the induced depression. Quantification of inflammatory mediators (IL-10, IL-4, IL-6, IL-1β, and TNF-α) in the brain demonstrated that BbHA and BbMe effectively decreased the effect of LPS on the brain concentration of all measured cytokines. Conclusions: Bauhinia blakeana produced an antidepressant effect, while BbMe also exerted a modulating effect, on the damage induced by LPS. Rutin, a glycosylated flavonoid, was identified as the main compound in the active fraction, which could mediate in the antidepressant and immunomodulatory effect.


2015 ◽  
Vol 223 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Christina Leibrock ◽  
Michael Hierlmeier ◽  
Undine E. Lang ◽  
Florian Lang

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.


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