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.

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.

scholarly journals The Endogenous Cannabinoid and the Nitricoxidergic Systems Differently Influence Heat and Cold Stress-Induced Analgesia

2021 ◽  
Vol 48 (1) ◽  
pp. 34-39
Author(s):  
H. Nocheva ◽  
Z. Sabit ◽  
E. Grigorov
Keyword(s):  
Cold Stress ◽  
Pain Perception ◽  
Cannabinoid Receptor ◽  
No Donor ◽  
Heat And Cold Stress ◽  
Male Wistar Rats ◽  
Nos Inhibitor ◽  
Mechanisms Of Development ◽  
Endogenous Cannabinoid

Abstract Stress-induced analgesia (SIA) is a well-known phenomenon, in which mechanisms of development opioid and non-opioid components take part. The endogenous cannabinoid system (ECS) takes part in the non-opioid pathways and modulates nociception. Nitric oxide (NO) is also proverbial to interfere with pain perception. The present study was performed to investigate the effects from interaction between the ECS and NO after heat (heat stress) or cold (cold stress) exposure. Male Wistar rats subjected to one hour of heat or cold stress were injected with different combinations of cannabinoid receptor type 1 (CB1) agonist anandamide (AEA) or antagonist (AM251) along with NO-donor, NO-precursor or inhibitor of the NO-synthase (NOS). Nociception was evaluated using Paw pressure (Randall-Selitto) test. The results showed that AEA-administration immediately after the end of stress let to a tendency to increase cold-SIA, but decreased heat-SIA. AEA along with NO-donor increased both cold- and heat-SIA but to a different degree. AM251 and NOS-inhibitor decreased SIA. Our experiments confirmed that the endogenous cannabinoid and the nitricoxidergic systems interact between them in the modulation of SIA. The ECS exerts a more prominent influence on cold rather than heat SIA. Differences in modulation probably depend on the type of stress, due to the different participation of ECS in the mechanisms of SIA development.

The Effect of Cannabidiol Coated by Nano-Chitosan on Learning and Memory, Hippocampal CB1 and CB2 Levels, and Amyloid Plaques in an Alzheimer’s Disease Rat Model

2021 ◽  
pp. 1-13
Author(s):  
Mohammadali Amini ◽  
Zohreh Abdolmaleki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Expression ◽  
Learning And Memory ◽  
Rat Model ◽  
Cannabinoid Receptor ◽  
Amyloid Plaques ◽  
Receptor Type ◽  
Cannabinoid Receptor Type 1

<b><i>Introduction:</i></b> Using nanoparticle (NP) drugs can have better effects on the target tissue in various diseases. Alzheimer’s disease (AD) is one of the degenerative neurological diseases that due to its high prevalence, requires the use of more appropriate treatments. Therefore, the aim of this study was consideration of the effect of cannabidiol (CBD) coated by nano-chitosan on learning and memory, hippocampal cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 1 (CB2) levels, and amyloid plaques in an AD rat model. <b><i>Material and Methods:</i></b> Thirty-five male Wistar rats were randomly divided into 5 groups (<i>n</i> = 7 in each): control, Alzheimer’s disease model that received the beta-amyloid (Aβ) peptide (Alz), Alz + nano-chitosan (NP) Alz + CBD, and Alz + NP + CBD. Alz was induced by injection of the Aβ1-42 peptide into the hippocampal area cornu ammonis1. After confirmation of Alz, 1 μL of CBD and NP + CBD were administered by oral gavage daily in rats for 1 month. The Morris water maze (MWM) test was used to assess learning and memory of animals. Cresyl violet staining was used for consideration of dead cells. Gene and protein expression of CB1 and CB2 was performed by real-time PCR and immunohistochemistry methods. <b><i>Results:</i></b> Induction of Alz significantly increased Aβ plaques and dead cells compared to the control group (<i>p</i> &#x3c; 0.001). Results of MWM in the day test show that Alz + NP + CBD significantly decrease escape latency (<i>p</i> &#x3c; 0.01), travelled distance (<i>p</i> &#x3c; 0.001), and significantly increased spending time (<i>p</i> &#x3c; 0.001) compared to the Alz group. Protein expression of CB1 and CB2 significantly increased in Alz + CBD and Alz + NP + CBD compared to the Alz group (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> It seems that CBD coated by nano-chitosan has good potential for reducing Aβ plaques, increasing brain CB1 and levels CB2, and improving learning and memory in Alz rats.

Kupffer cell-initiated remote hepatic injury following bilateral hindlimb ischemia is complement dependent

2001 ◽  
Vol 280 (2) ◽  
pp. G279-G284 ◽  
Author(s):  
Robert W. Brock ◽  
Robert G. Nie ◽  
Kenneth A. Harris ◽  
Richard F. Potter
Keyword(s):  
Kupffer Cell ◽  
Kupffer Cells ◽  
Hepatic Injury ◽  
Cell Function ◽  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Hindlimb Ischemia ◽  
Male Wistar Rats ◽  
Stimulation Of

Intravital fluorescence microscopy was applied to the livers of male Wistar rats to test the hypothesis that complement mobilization stimulates Kupffer cells and subsequently initiates hepatic injury after hindlimb ischemia/reperfusion (I/R). Following 3 h of limb reperfusion, hepatocellular viability (serum levels of alanine transaminase and cell death via propidium iodide labeling) decreased significantly from levels in sham-operated animals. Inhibition of complement mobilization with soluble complement receptor type 1 (20 mg/kg body wt) and interruption of Kupffer cell function with GdCl3 (1 mg/100g body wt) resulted in significant hepatocellular protection. Although the effects of hindlimb I/R on hepatic microvascular perfusion were manifest as increased heterogeneity, both complement inhibition and suppression of Kupffer cell function resulted in marked improvements. No additional hepatocellular protection and microvascular improvements were provided by combining the interventions. Furthermore, inhibition of complement mobilization significantly depressed Kupffer cell phagocytosis by 42% following limb reperfusion. These results suggest that the stimulation of Kupffer cells via complement mobilization is necessary but is not the only factor contributing to the early pathogenesis of hepatic injury following hindlimb I/R.

scholarly journals Acute Administration of Caffeine: The Effect on Motor Coordination, Higher Brain Cognitive Functions and the Social Behavior of BLC57 Mice

2018 ◽  
Author(s):  
Sayed Almosawi ◽  
Hasan Baksh ◽  
Abdulrahman Qareeballah ◽  
Faisal Falamarzi ◽  
Bano Alsaleh ◽  
...  
Keyword(s):  
Social Behavior ◽  
Learning And Memory ◽  
Dose Group ◽  
Motor Coordination ◽  
Control Group ◽  
High Dose ◽  
Acute Administration ◽  
Moderate Dose ◽  
The Social ◽  
High Doses

Heavy caffeine consumption is associated with adverse health effects. The effects of moderate and high doses of caffeine mixed with drinking water on the motor coordination, learning and memory and the social behavior in mice were studied in mice. Animals were divided into 3 groups: control group, moderate dose group (Ac MD) and high dose group (Ac HD). The animals were tested after 7 days of caffeine administration. Rota rod test for motor coordination showed that the mice of the moderate dose group could stay more time on the rotating rod before they fall than the control group and the high dose group. Water maze test for learning and memory showed better performance of mice receiving moderate dose of caffeine compared to the other groups. Animals that were administered moderate as well as high doses of caffeine showed no sociability and no preference for social novelty in the three-chamber test used to test the social behavior. In elevated plus maze, control animals showed no anxiety- like behavior while mice administered with caffeine were both showing anxiety-like behaviors. We concluded that acute administration of moderate dose of caffeine to mice could enhance their spatial memory and motor coordination. High doses however caused defects in memory and learning. The social behavior as the level of anxiety and sociability was affected negatively by moderate as well as high dose caffeine administration.

scholarly journals Interactions between the cannabinoid and the serotonergic systems in modulation of pain perception

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 109-115
Author(s):  
Hristina Nocheva ◽  
Zafer Sabit ◽  
Dimitar Bakalov ◽  
Evgeni Grigorov
Keyword(s):  
Heat Stress ◽  
Pain Perception ◽  
Cannabinoid Receptor ◽  
Mediating Effect ◽  
Serotonergic System ◽  
Intact Male ◽  
Pressure Test ◽  
Male Wistar Rats ◽  
Intact Rats

The aim of our study was to evaluate the effects of cannabinoids and serotonergic system on nociception in intact rats and after heat stress. Cannabinoid receptor type 1 (CB1) and 5-hydroxytryptamine receptor (5НТ1А) agonists and antagonists have been administered according to different experimental designs (alone and in combinations) in intact male Wistar rats, as well in animals subjected to one hour of heat stress. Pain perception has been evaluated by Paw pressure test. Our results pointed out that cannabinoids and the serotonergic system interact in nociception in intact animals as well as after heat stress. Cannabinoids seemed to have less prominent role in such interaction in intact animals than after heat stress. The interplay between the two systems probably involves different mechanisms in intact animals and after heat stress with time-dependent effects. The interaction between the cannabinoid and the serotonergic systems exerts a modulating rather than mediating effect on h-SIA.

Impact of buprenorphine on learning and memory ability, oxidative status and inflammation in the hippocampus of rat

2020 ◽  
Vol 13 ◽  
Author(s):  
Mohammad Samini ◽  
Tahereh Farkhondeh ◽  
Mohsen Azimi-Nezhad ◽  
Saeed Samarghandian
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Cellular Damage ◽  
Control Group ◽  
Inflammatory Parameters ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Synthetic Derivative ◽  
High Doses ◽  
Factor Α

Aims: This study was designed to investigate the effects of low and high doses of BUP on oxidative and inflammatory indices in the hippocampus and learning and memory behavior in an animal model. Background: Buprenorphine (BUP) a “synthetic derivative of the opioid alkaloid thebaine” may be associated with cellular damage in the central nervous system. Objective: The association between BUP administration and oxidative and inflammatory damage and also learning and memory impairment is not clear. Method: For this reason, twenty four male Wistar rats were randomly allocated in to one control and two BUP-treated groups (0.3 and 1 mg/kg, SC), (n=8, for each group). After 4 weeks, learning and memory abilities were assessed by using Y-maze test. Then, oxidative stress indices including glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were assessed in the serum and hippocampus of each animal by using spectrophotometer. Inflammatory parameters such tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were also measured in the serum and hippocampus of rats by using ELISA. Results: The present findings indicated that the memory and learning time was lengthened in BUP (1mg/kg)-treated rats versus control animals (p<0.05). Additionally, it was observed that BUP (1 mg/kg) significantly increased the serum and hippocampal levels of MDA and TNF-α and also decreased GSH levels versus the control group (p< 0.05). Conclusion: The present results reveal that BUP may cause learning and memory dysfunction via inducing oxidative stress and inflammation in hippocampus.

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.

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