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

2021 ◽  
Author(s):  
Gabriela Pandini Silote ◽  
Michelle C. Gatto ◽  
Amanda Eskelund ◽  
Francisco S. Guimarães ◽  
Gregers Wegener ◽  
...  
Keyword(s):  
Selective Breeding ◽  
Cannabis Sativa ◽  
Tail Suspension Test ◽  
Rodent Models ◽  
Resistant Lines ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Administration Time ◽  
Different Strains ◽  
Different Doses

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.

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 ◽  
...  
Keyword(s):  
Selective Breeding ◽  
Cannabis Sativa ◽  
Tail Suspension Test ◽  
Rodent Models ◽  
Tail Suspension ◽  
Resistant Lines ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Administration Time ◽  
Different Strains

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.

scholarly journals Δ3,2-Hydroxybakuchiol Attenuates Depression in Multiple Rodent Models Possibly by Inhibition of Monoamine Transporters in Brain

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Gang Zhao ◽  
Li-he Guo ◽  
Wei Huang ◽  
Jia-liang Hu
Keyword(s):  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Rat Striatum ◽  
Mild Stress ◽  
Monoamine Transporters ◽  
Rodent Models ◽  
Norepinephrine Concentration ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Pheochromocytoma Pc12

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.

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.

Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala

2011 ◽  
Vol 23 (5) ◽  
pp. 241-248 ◽  
Author(s):  
Gislaine Z. Réus ◽  
Roberto B. Stringari ◽  
Karine F. Ribeiro ◽  
Tatiana Luft ◽  
Helena M. Abelaira ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Forced Swimming Test ◽  
Cannabis Sativa ◽  
Field Tests ◽  
Brain Derived Neurotrophic Factor ◽  
Chemical Constituent ◽  
Forced Swimming ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Swimming Test

Réus GZ, Stringari RB, Ribeiro KF, Luft T, Abelaira HM, Fries GR, Aguiar BW, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala.Objective: Cannabidiol is a chemical constituent from Cannabis sativa and it has multiple mechanisms of action, including antidepressant effects. The main objective of the present study was to evaluate behavioural and molecular effects induced by administration of cannabidiol and imipramine in rats.Methods: In the present study, rats were acutely or chronically treated for 14 days once a day with saline, cannabidiol (15, 30 and 60 mg/kg) or imipramine (30 mg/kg) and the animals behaviour was assessed in forced swimming and open-field tests. Afterwards, the prefrontal cortex, hippocampus and amygdala brain-derived neurotrophic factor (BDNF) levels were assessed by enzyme-linked immunosorbent sandwich assay.Results: We observed that both acute and chronic treatments with imipramine at the dose of 30 mg/kg and cannabidiol at the dose of 30 mg/kg reduced immobility time and increased swimming time; climbing time was increased only with imipramine at the dose of 30 mg/kg, without affecting locomotor activity. In addition, chronic treatment with cannabidiol at the dose of 15 mg/kg and imipramine at the dose of 30 mg/kg increased BDNF levels in the rat amygdala.Conclusion: In conclusion, our results indicate that cannabidiol has an antidepressant-like profile and could be a new pharmacological target for the treatment of major depression.

Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

2020 ◽  
Vol 16 (9) ◽  
pp. 1319-1327
Author(s):  
Ferdous Khan ◽  
Syed A. Kuddus ◽  
Md. H. Shohag ◽  
Hasan M. Reza ◽  
Murad Hossain
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reduced Glutathione ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Glutathione Depletion ◽  
Swim Test ◽  
Stress Markers ◽  
Immobility Time ◽  
Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

scholarly journals Ketamine—50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms

2021 ◽  
Vol 73 (2) ◽  
pp. 323-345
Author(s):  
Samuel Kohtala
Keyword(s):  
Traumatic Stress ◽  
Molecular Mechanisms ◽  
Post Traumatic Stress ◽  
Active Metabolites ◽  
The Past ◽  
Antidepressant Effects ◽  
Post Traumatic ◽  
Pharmacologically Active ◽  
Dose Dependent ◽  
Different Doses

AbstractOver the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.

scholarly journals Selective cannabis strain allergy in a patient presenting with a local allergic reaction

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Peter Stepaniuk ◽  
Amin Kanani
Keyword(s):  
Direct Contact ◽  
Cannabis Sativa ◽  
Skin Prick Testing ◽  
Case Presentation ◽  
Published Report ◽  
Cannabis Indica ◽  
Different Strains ◽  
Allergen Identification ◽  
Strain Dependent ◽  
Fresh Skin

Abstract Background Cannabis use is growing domestically due to recent legalization in many jurisdictions. There are two main species of cannabis, Cannabis sativa and Cannabis indica, and thousands of different commercially available cannabis strains. Although there are multiple reports of cannabis allergy in the literature, to our knowledge, there is no prior published report of selective cannabis strain allergy. Case presentation A 31-year-old male was referred for allergy assessment due to several episodes of localized pruritus and erythema after direct contact with various strains of cannabis. He had noted that the severity of his reaction appeared to be strain dependent. He developed a severe local reaction involving bilateral periorbital edema shortly after coming into direct contact with one particular strain of cannabis. He denied any adverse symptoms after inhalation of cannabis. Fresh skin prick testing was performed to various strains of cannabis and had positive testing to the three of the five tested strains. Conclusions We believe this is the first reported case of selective cannabis strain allergy based on patient history and skin prick testing. This case report outlines the variability in different strains of cannabis and stresses the importance of further research into cannabis allergen identification. Multiple cannabis allergens should be included and incorporated into commercial extracts when they become routinely available.

Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hossein Omidi-Ardali ◽  
Abolfazl Ghasemi Badi ◽  
Elham Saghaei ◽  
Hossein Amini-Khoei
Keyword(s):  
Nitric Oxide ◽  
Effective Dose ◽  
Animal Studies ◽  
Tail Suspension Test ◽  
Forced Swimming ◽  
Antidepressant Effect ◽  
Tail Suspension ◽  
Immobility Time ◽  
Swimming Test ◽  
Underlying Mechanisms

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.

The Effect of Fluoxetine and Ibuprofen on BCG-Induced Alteration in Pain Sensitivity in Mice

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Heba H El-Morsy ◽  
Wesam El-Bakly ◽  
Amany H Hasanin ◽  
May Hamza ◽  
M Abdel-Bary
Keyword(s):  
Drinking Water ◽  
Mechanical Allodynia ◽  
Formalin Test ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Control Group ◽  
Base Line ◽  
Immobility Time ◽  
Long Time ◽  
Incisional Pain

Abstract Clinical observations recognized the co-existence and interactions of pain and depression a long time, ago. The aim of this work was to study the effect of ibuprofen and fluoxetine on BCGinduced depressive-like behaviour, on formalin-induced pain, as well as on mechanical allodynia after planter incision in mice. BCG induced a depressive behaviour that was seen in the forced swim test (FST) and the tail suspension test (TST). It also induced a decrease in pain-related behaviour in the formalin test, and an increase in the baseline in mechanical allodynia test compared to the control group. Fluoxetine (80 mg/L of drinking water) showed a significant decrease in the immobility time in the FST and TST and enhanced pain related behaviour in formalin test in the BCG-inoculated group. However, it did not affect the increase in the pain threshold in the planter incision allodynia model. Adding ibuprofen to drinking water (0.2 g/L of drinking water), reversed the depressive like behaviour induced by BCG and enhanced pain-related behaviour in formalin test, in both the total pain-related behaviour and phase 2. It also prevented the increase in the base line induced by BCG. On the other hand, the incisional pain model was not affected by BCG inoculation except at the 2-hour time point, where it showed hypoalgesia, as well.

scholarly journals Mouse, rat, and dog bioavailability and mouse oral antidepressant efficacy of (2R,6R)-hydroxynorketamine

2018 ◽  
Vol 33 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Jaclyn N Highland ◽  
Patrick J Morris ◽  
Panos Zanos ◽  
Jacqueline Lovett ◽  
Soumita Ghosh ◽  
...  
Keyword(s):  
Oral Administration ◽  
Learned Helplessness ◽  
Oral Bioavailability ◽  
Forced Swim Test ◽  
Abuse Potential ◽  
Absolute Bioavailability ◽  
Forced Swim ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Antidepressant Efficacy

Background: ( R,S)-ketamine has gained attention for its rapid-acting antidepressant actions in patients with treatment-resistant depression. However, widespread use of ketamine is limited by its side effects, abuse potential, and poor oral bioavailability. The ketamine metabolite, ( 2R,6R)-hydroxynorketamine, exerts rapid antidepressant effects, without ketamine’s adverse effects and abuse potential, in rodents. Methods: We evaluated the oral bioavailability of ( 2R,6R)-hydroxynorketamine in three species (mice, rats, and dogs) and also evaluated five candidate prodrug modifications for their capacity to enhance the oral bioavailability of ( 2R,6R)-hydroxynorketamine in mice. Oral administration of ( 2R,6R)-hydroxynorketamine was assessed for adverse behavioral effects and for antidepressant efficacy in the mouse forced-swim and learned helplessness tests. Results: ( 2R,6R)-hydroxynorketamine had absolute bioavailability between 46–52% in mice, 42% in rats, and 58% in dogs. Compared to intraperitoneal injection in mice, the relative oral bioavailability of ( 2R,6R)-hydroxynorketamine was 62%, which was not improved by any of the candidate prodrugs tested. Following oral administration, ( 2R,6R)-hydroxynorketamine readily penetrated the brain, with brain to plasma ratios between 0.67–1.2 in mice and rats. Oral administration of ( 2R,6R)-hydroxynorketamine to mice did not alter locomotor activity or precipitate behaviors associated with discomfort, sickness, or stereotypy up to a dose of 450 mg/kg. Oral ( 2R,6R)-hydroxynorketamine reduced forced-swim test immobility time (15–150 mg/kg) and reversed learned helplessness (50–150 mg/kg) in mice. Conclusions: These results demonstrate that ( 2R,6R)-hydroxynorketamine has favorable oral bioavailability in three species and exhibits antidepressant efficacy following oral administration in mice.

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