scholarly journals Strain-, Sex-, and Time-Dependent Antidepressant-like Effects of Cannabidiol

2021 ◽  
Vol 14 (12) ◽  
pp. 1269
Author(s):  
Gabriela P. Silote ◽  
Michelle C. Gatto ◽  
Amanda Eskelund ◽  
Francisco S. Guimarães ◽  
Gregers Wegener ◽  
...  

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behavior. Moreover, only a few studies investigated the effect of CBD in female rodents. Therefore, we aimed to (i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects and (ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect 1 h post injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at 1 h and decreasing it at 2 h. In conclusion, strain, sex, and administration time affect CBD’s behavioral response to rodents exposed to tests predictive of antidepressant effects.

Author(s):  
Gabriela Pandini Silote ◽  
Michelle C. Gatto ◽  
Amanda Eskelund ◽  
Francisco S. Guimarães ◽  
Gregers Wegener ◽  
...  

Cannabidiol (CBD) is a non-intoxicating compound extracted from Cannabis sativa, showing antidepressant-like effects in different rodent models. However, inconsistent results have been described depending on the species and the strain used to assess depressive-like behaviour. Moreover, only a few studies have investigated the effect of CBD in female rodents. Therefore, we aimed to i) investigate the effects of CBD in two different strains of mice (Swiss and C57BL/6) and in a rat model of depression based on selective breeding (Flinders Sensitive and Resistant Lines, FSL and FRL) subjected to tests predictive of antidepressant-like effects; and ii) investigate the influence of sex in the effects of CBD in both mice and rats. CBD induced an antidepressant-like effect in male Swiss but not in female Swiss or C57BL/6 mice in the tail suspension test (TST). In male FSL rats, CBD produced an antidepressant-like effect one-hour post-injection. However, in female FSL, CBD induced a bimodal effect, increasing the immobility time at one hour and decreasing it at two hours. Ketamine produced an antidepressant-like effect in male and female FSL rats at different doses. In conclusion, strain, sex, and administration time affect CBD's behavioural response to rodents exposed to tests predictive of antidepressant effects.


2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Gang Zhao ◽  
Li-he Guo ◽  
Wei Huang ◽  
Jia-liang Hu

Δ3,2-Hydroxybakuchiol is isolated fromPsoralea corylifolia (L.), which has therapeutic applications in traditional Chinese medicine. Our previous studies have showed that Δ3,2-hydroxybakuchiol inhibited the decreased activity of reserpinized mice, suggestive of its antidepressive potential. In this study, we explored the antidepressant profile of Δ3,2-hydroxybakuchiol in various rodent models and its possible monoamine-modulating mechanism. Δ3,2-Hydroxybakuchiol significantly reduced immobility time of mice in forced swim test and tail suspension test. Δ3,2-Hydroxybakuchiol also significantly increased sucrose consumption in chronic unpredictable mild stress (CUMS) rat model. Furthermore, isotope uptake study showed that Δ3,2-hydroxybakuchiol inhibited the activity of human dopamine transporter (DAT) and norepinephrine transporter (NET) in transporter-overexpressing pheochromocytoma (PC12) cells with IC50values similar to the potency of bupropion. Microdialysis showed that Δ3,2-hydroxybakuchiol increased dopamine and norepinephrine concentration in rat striatum. In summary, Δ3,2-hydroxybakuchiol exerts antidepressant effects on various types of depression models through a possible mechanism of monoamine transporter inhibition.


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.


2019 ◽  
pp. 01-12
Author(s):  
Rui Li ◽  
Wai-Kin Mat ◽  
Wing-Man Chan ◽  
T Yiu-Cheong Ho ◽  
Rigil K Yeung ◽  
...  

The racemate dl-tetrahydropalmatine (dl-THP) is known for its analgesic and sedative effects, and has been shown by us to be a potential agent for the treatment of anxiety.Herein, to delineate the therapeutic potentials of its different isomeric forms, the behavioral effects of l-THP, dl-THP and d-THP were compared regarding their anxiolytic and antidepressant properties in mouse behavioral models using the elevated plus-maze test and tail suspension test respectively. The anxiolytic and antidepressant effects of both l-THP and dl-THP were evident in forty-five minutes following oral administration. Moreover, l-THP exhibited much greater anxiolytic potency in the elevated plus-maze (0.1-2.5 mg/kg) and antidepressant potency in the tail suspension test (0.5-5.0 mg/kg) than dl-THP, whereas d-THP was inactive in either of these tests. As well, l-THP enhanced sociability and preference for social novelty at 0.1-0.5 mg/kg in Crawley’s three-chamber behavioral tests, and inhibited the amphetamine-induced manic-like hyperactivity of amphetamine-sensitized mice at 0.05-0.2 mg/kg. These pharmacological actions of l-THP were unaccompanied by any significant locomotor or myorelaxant side-effects. Co-administration of flumazenil, a GABAA receptor antagonist, inhibited the anxiolytic and antidepressant effects of l-THP, even though the binding affinity of l-THP was higher for dopamine D2-like receptors than for GABAA receptors. On this basis, l-THP displayed potential as a fast-acting drug for the treatment of anxiety, depression and bipolar disorder. Keywords: l-THP; dl-THP; Anxiolysis; Antidepressant; GABAA receptor; Fast-acting


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.


Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989126 ◽  
Author(s):  
Hafiz Muhammad Asif ◽  
Abdul Hayee ◽  
Muhammad Rahil Aslam ◽  
Khalil Ahmad ◽  
Abdul Sattar Hashmi

The present work was carried out to assess the Onosma bracteatum anxiolytic and antidepressant properties. Swiss albino mice (male) were fed orally with hydroalcoholic extract at different doses 50, 100, and 200 mg 1 hour prior to test with the standard diazepam and fluoxetine. Anxiolytic and antidepressant activities were evaluated by using open field, elevated plus maze, force swimming, and tail suspension test. Results of open field test showed an increase in number of line crossing as well as number of rearing in dosage-dependent design. Although results of elevated plus maze test evidently showed antianxiety effect of O bracteatum by increasing the time spent in open arms along with decreasing the time spent in closed arms in dosage-dependent way. For the evaluation of antidepressant effect, O bracteatum diminished the immobility time and expanded mobility time in forced swim model in dosage-dependent way. Likewise, O bracteatum expanded time span of mobility along with diminished immobility time in tail suspension method in dosage-dependent way. Outcome demonstrated that plant at the dose of 200 mg/kg body weight showed significant potential which was similar to that standard diazepam and fluoxetine. Hence, O bracteatum may be used as potent natural psychotherapeutic agent against the mental disorders.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Ming Zhong ◽  
Xiaoting Tian ◽  
Shuoji Chen ◽  
Mingcang Chen ◽  
Ziqiong Guo ◽  
...  

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.


Author(s):  
Ismail O. Ishola ◽  
Olufunsho Awodele ◽  
Chinedum O. Eluogu

Abstract:: HeMI (12.5–100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM).: HeMI (12.5–100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, p<0.001], [F(6,56)=7.55, p<0.001] in the FST and TST, respectively. Moreover, co-administration of sub-therapeutic doses of imipramine or fluoxetine with HeMI (3.125 mg/kg) elicited significant reduction in time spent immobile in the FST. However, pretreatment of mice with parachlorophenylalanine, metergoline, yohimbine or sulpiride abolished the antidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, p<0.001] increase in open arms exploration by 75.55 % and this effect was blocked by pretreatment of mice with flumazenil or metergoline.: Findings from this study showed antidepressant-like effect of


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.


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