scholarly journals Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 792 ◽  
Author(s):  
Graziela Vieira ◽  
Juliana Cavalli ◽  
Elaine C. D. Gonçalves ◽  
Saulo F. P. Braga ◽  
Rafaela S. Ferreira ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
D2 Receptor ◽  
Inverse Agonist ◽  
Control Group ◽  
Molecular Evidence ◽  
Acute Administration ◽  
Immobility Time ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100–200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence.

Effects of cannabinoid and vanilloid receptor agonists and their interaction on learning and memory in rats

2017 ◽  
Vol 95 (4) ◽  
pp. 382-387 ◽  
Author(s):  
Mariam Shiri ◽  
Alireza Komaki ◽  
Shahrbanoo Oryan ◽  
Masoumeh Taheri ◽  
Hamidreza Komaki ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Cannabinoid Receptor ◽  
Vanilloid Receptor ◽  
Interactive Effects ◽  
Control Group ◽  
Acute Administration ◽  
Male Wistar Rats ◽  
Agonistic Effect ◽  
Stimulation Of

Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212–2, (3) capsaicin, and (4) WIN55,212–2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212–2, a cannabinoid receptor (CB1/CB2) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212–2 (CB1/CB2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212–2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats’ cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212–2 on learning and memory.

Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat

Neuroreport ◽  
1997 ◽  
Vol 8 (2) ◽  
pp. 491-496 ◽  
Author(s):  
Miguel Navarro ◽  
Elena Hernández ◽  
Raúl M. Muñoz ◽  
Ignacio del Arco ◽  
María Angeles Villanúa ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cannabinoid Receptor ◽  
Acute Administration ◽  
Cb1 Cannabinoid Receptor ◽  
Sr 141716A

scholarly journals CB1 Receptor-Dependent and Independent Induction of Lipolysis in Primary Rat Adipocytes by the Inverse Agonist Rimonabant (SR141716A)

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 896 ◽  
Author(s):  
Günter A. Müller ◽  
Andreas W. Herling ◽  
Susanne Wied ◽  
Timo D. Müller
Keyword(s):  
Cannabinoid Receptor ◽  
Inverse Agonist ◽  
Hormone Sensitive Lipase ◽  
Acute Administration ◽  
Free System ◽  
Peripheral Tissues ◽  
Rat Adipocytes ◽  
A Cell ◽  
High Concentrations ◽  
Stimulation Of

(1) Background: Acute administration of the cannabinoid receptor 1 (CB1R) inverse agonist Rimonabant (SR141716A) to fed Wistar rats was shown to elicit a rapid and short-lasting elevation of serum free fatty acids. (2) Methods: The effect of Rimonabant on lipolysis in isolated primary rat adipocytes was studied to raise the possibility for direct mechanisms not involving the (hypothalamic) CB1R. (3) Results: Incubation of these cells with Rimonabant-stimulated lipolysis to up to 25% of the maximal isoproterenol effect, which was based on both CB1R-dependent and independent mechanisms. The CB1R-dependent one was already effective at Rimonabant concentrations of less than 1 µM and after short-term incubation, partially additive to β-adrenergic agonists and blocked by insulin and, in part, by adenosine deaminase, but not by propranolol. It was accompanied by protein kinase A (PKA)-mediated association of hormone-sensitive lipase (HSL) with lipid droplets (LD) and dissociation of perilipin-1 from LD. The CB1R-independent stimulation of lipolysis was observed only at Rimonabant concentrations above 1 µM and after long-term incubation and was not affected by insulin. It was recapitulated by a cell-free system reconstituted with rat adipocyte LD and HSL. Rimonabant-induced cell-free lipolysis was not affected by PKA-mediated phosphorylation of LD and HSL, but abrogated by phospholipase digestion or emulsification of the LD. Furthermore, LD isolated from adipocytes and then treated with Rimonabant (>1 µM) were more efficient substrates for exogenously added HSL compared to control LD. The CB1R-independent lipolysis was also demonstrated in primary adipocytes from fed rats which had been treated with a single dose of Rimonabant (30 mg/kg). (4) Conclusions: These data argue for interaction of Rimonabant (at high concentrations) with both the LD surface and the CB1R of primary rat adipocytes, each leading to increased access of HSL to LD in phosphorylation-independent and dependent fashion, respectively. Both mechanisms may lead to direct and acute stimulation of lipolysis at peripheral tissues upon Rimonabant administration and represent targets for future obesity therapy which do not encompass the hypothalamic CB1R.

Expression of Cannabinoid Receptors on the Neoplastic Lymphocytes in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4804-4804
Author(s):  
Jaroslaw A. Piszcz ◽  
Miroslawa Pietruczuk ◽  
Janusz S. Kloczko ◽  
Milena Dabrowska ◽  
Marzenna Galar ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Cannabinoid Receptors ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Neoplastic Cells ◽  
Fluorescent Intensity ◽  
Cb2 Receptors ◽  
Neoplastic Lymphocytes ◽  
Cb1 And Cb2 Receptors

Abstract Endocannabinoids take part in the physiology of neural and immune systems. The latest data showed that these compounds and their receptors play an important role in proliferation and apoptosis of various neoplastic cells. Cannabinoids were shown to increase apoptosis in human leukemia and lymphoma cell lines and culture of neoplastic cells obtained from patients with T-cell acute lymphoblastic leukemia. The aim of the study was an assessment of cannabinoid receptors expression on lymphocytes B derived from patients with CLL. The study group contains newly diagnosed, untreated adult patients with B-cell chronic lymphocytic leukemia; 13 male and 7 female, aged from 44 to 65. All of the patients were in B or C stage according to Binet. Peripheral blood samples from 10 healthy adult donors were used as the control group. The patients were hospitalized in the Department of Haematology, Medical University in Bialystok, Poland. Diagnosis of CLL in all cases was confirmed by routine immunophenotyping study. For flow cytometric analysis 1x105 – 1x106 of peripheral blood cells were incubated with 10ul of anty CB1 and anty CB2 polyclonal antibodies (American Diagnostics). Then 10ul of monoclonal antibodies IgG1-FITC and CD19-PE (Becton Dickinson) were added and the samples were incubated for 20 min in dark in 4°C. The samples were lysed, fixed and stabilized using Immuno-Prep (Coulter procedure) and assessed by flaw cytometry (Epics XL, Coulter). Statistical analysis was performed using non parametric U Mann-Whitney and Wilcoxon Tests. The conducted study revealed high expression of CB1 and CB2 receptors on the surface of neoplastic lymphocytes. The percentage of CB1/CD19 and CB2/CD19 positive cells in CLL patients were significantly higher, compared to the control group respectively (81.2±9,8% vs 12.0±9,3% p<0,05; 94,8±11,0 % vs 9,9±4,0%, p<0,05). No difference was noticed between the percentage of lymphocytes with CB1 and CB2 receptors expression in CLL and control group. Fluorescent intensity of CB2 receptors was about ten folds higher than CB1 receptors in both groups. The study demonstrated the presence of both types of cannabinoid receptors (CB1 and CB2) on neoplastic cells derived from patients with chronic lymphocytic leukemia. The higher percentage of B-lymphocytes expressing cannabinoid receptors in CLL patient suggests that the cannabinoid system may take part in CLL development. High intensity of CB2 receptor may be another target in CLL treatment.

scholarly journals Functional characterization of the novel cannabinoid receptor GPR55 and its modulation by CB1 and CB2 receptors

2008 ◽  
Vol 8 (Suppl 1) ◽  
pp. A23
Author(s):  
Nariman Balenga ◽  
Julia Kargl ◽  
Christopher M Henstridge ◽  
Andrew J Irving ◽  
Maria Waldhoer
Keyword(s):  
Cannabinoid Receptor ◽  
Functional Characterization ◽  
The Novel ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

GPR55 – a putative “type 3” cannabinoid receptor in inflammation

2016 ◽  
Vol 27 (3) ◽  
Author(s):  
Hyewon Yang ◽  
Juan Zhou ◽  
Christian Lehmann
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Signaling System ◽  
Broad Distribution ◽  
Potential Therapeutic Target ◽  
Cellular Processes ◽  
Cb2 Receptors ◽  
Type 3 ◽  
G Protein Coupled ◽  
Cb1 And Cb2 Receptors

AbstractG protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3” cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.

Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors

2016 ◽  
Vol 94 (6) ◽  
pp. 599-612 ◽  
Author(s):  
Arya Haj-Mirzaian ◽  
Nastaran Kordjazy ◽  
Sattar Ostadhadi ◽  
Shayan Amiri ◽  
Arvin Haj-Mirzaian ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Physical Stress ◽  
Acute Administration ◽  
Mk 801 ◽  
Behavioral Despair ◽  
Immobility Time

Opioid and N-methyl-d-aspartate (NMDA) receptors mediate different effects of fluoxetine. We investigated whether opioid and NMDA receptors are involved in the protective effect of fluoxetine against the behavioral despair induced by acute physical stress in male mice. We used the forced swimming test (FST), tail suspension test (TST), and open-field test (OFT) for behavioral evaluation. We used fluoxetine, naltrexone (opioid receptor antagonist), MK-801 (NMDA receptor antagonist), morphine (opioid receptor agonist), and NMDA (NMDA receptor agonist). Acute foot-shock stress (FSS) significantly induced behavioral despair (depressive-like) and anxiety-like behaviors in tests. Fluoxetine (5 mg/kg) reversed the depressant-like effect of FSS, but it did not alter the locomotion and anxiety-like behavior in animals. Acute administration of subeffective doses of naltrexone (0.3 mg/kg) or MK-801 (0.01 mg/kg) potentiated the antidepressant-like effect of fluoxetine, while subeffective doses of morphine (1 mg/kg) and NMDA (75 mg/kg) abolished this effect of fluoxetine. Also, co-administration of subeffective doses of naltrexone (0.05 mg/kg) and MK-801 (0.003 mg/kg) with fluoxetine (1 mg/kg) induced a significant decrease in the immobility time in FST and TST. Our results showed that opioid and NMDA receptors (alone or in combination) are involved in the antidepressant-like effect of fluoxetine against physical stress.

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