Tag Archives: CB1

Effects of CP 55,940–agonist of CB1 cannabinoid receptors on ghrelin and somatostatin producing cells in the rat pancreas.

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“Cannabinoids participate in the modulation of numerous functions in the human organism, increasing the sense of hunger, affecting carbohydrate and lipid metabolism, and controlling systemic energy balance mechanisms. Moreover, they influence the endocrine system functions, acting via two types of receptors, CB1 and CB2. The aim of the present study was to examine the number, distribution and activity of ghrelin and somatostatin producing endocrine cells in the pancreas of rats after a single administration of selective CP 55,940 agonist of CB1 receptor. The study was performed on 20 rats. Neuroendocrine cells were identified by immunohistochemical reactions, involving specific antibodies against ghrelin and somatostatin. The distribution and number of ghrelin- and somatostatin-immunoreactive cells were separately studied in five pancreas islets of each section. A performed analysis showed a decreased number of somatostatin-immunoreactive cells and a weak immunoreactivity of ghrelin and somatostatin containing neuroendocrine cells in the pancreatic islets of experimental rats, compared to control animals. The obtained results suggest that a single administration of a selective CP 55,940 agonist of CB1 receptor influences the immunoreactivity of endocrine cells with ghrelin and somatostatin expression in the pancreas islets.”

http://www.ncbi.nlm.nih.gov/pubmed/22532145

Cannabinoids and anxiety.

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“The term cannabinoids encompasses compounds produced by the plant Cannabis sativa, such as delta9-tetrahydrocannabinol, and synthetic counterparts. Their actions occur mainly through activation of cannabinoid type 1 (CB1) receptors. Arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG) serve as major endogenous ligands (endocannabinoids) of CB1 receptors. Hence, the cannabinoid receptors, the endocannabinoids, and their metabolizing enzymes comprise the endocannabinoid system. Cannabinoids induce diverse responses on anxiety- and fear-related behaviors. Generally, low doses tend to induce anxiolytic-like effects, whereas high doses often cause the opposite. Inhibition of endocannabinoid degradation seems to circumvent these biphasic effects by enhancing CB1 receptor signaling in a temporarily and spatially restricted manner, thus reducing anxiety-like behaviors. Pharmacological blockade or genetic deletion of CB1 receptors, in turn, primarily exerts anxiogenic-like effects and impairments in extinction of aversive memories. Interestingly, pharmacological blockade of Transient Receptor Potential Vanilloid Type-1 (TRPV1) channel, which can be activated by anandamide as well, has diametrically opposite consequences. This book chapter summarizes and conceptualizes our current knowledge about the role of (endo)cannabinoids in fear and anxiety and outlines implications for an exploitation of the endocannabinoid system as a target for new anxiolytic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/21309120

The endocannabinoid system in anxiety, fear memory and habituation.

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“Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and fear has been accumulated, providing leads for novel therapeutic approaches. In anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic and anxiogenic responses have been obtained after both increases and decreases of the endocannabinoid tone. The recently developed genetic tools have revealed different but complementary roles for the cannabinoid type 1 (CB1) receptor on GABAergic and glutamatergic neuronal populations. This dual functionality, together with the plasticity of CB1 receptor expression, particularly on GABAergic neurons, as induced by stressful and rewarding experiences, gives the ECS a unique regulatory capacity for maintaining emotional homeostasis. However, the promiscuity of the endogenous ligands of the CB1 receptor complicates the interpretation of experimental data concerning ECS and anxiety. In fear memory paradigms, the ECS is mostly involved in the two opposing processes of reconsolidation and extinction of the fear memory. Whereas ECS activation deteriorates reconsolidation, proper extinction depends on intact CB1 receptor signalling. Thus, both for anxiety and fear memory processing, endocannabinoid signalling may ensure an appropriate reaction to stressful events. Therefore, the ECS can be considered as a regulatory buffer system for emotional responses.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267552/

Role of endocannabinoid system in the ventral hippocampus of rats in the modulation of anxiety-like behaviours.

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“The effects of unilateral intra-ventral hippocampus injection of URB597, a fatty acid amid hydrolase inhibitor, and AM251, a selective CB(1) receptor antagonist, on anxiety-related behaviours using elevated plus-maze test of anxiety were evaluated in the present study. Possible involvement of GABAergic system in those effects of URB597 was also evaluated. Injection of URB597 at the doses of 0.01, 0.1 and 1 microg/rat showed significant anxiogenic-like effects at 0.1 and 1 microg/rat. However, intra-ventral hippocampus injection of AM251 at the doses of 0.001, 0.01 and 0.1 microg/rat did not produce any significant effect in the elevated plus-maze. The ineffective doses of selective GABA(A) receptor antagonist, bicuculline (2 microg/rat) and selective GABA(B) receptor antagonist, phaclofen (1 microg/rat) on anxiety-related behaviours were also injected with URB597 (0.1 microg/rat). The present data showed that neither bicuculline nor phaclofen affected the anxiogenic-like effects of URB597. The results showed that injection of URB597 into the ventral hippocampus may be anxiogenic and GABAergic system may not be involved in its anxiogenic-like effects.”

http://www.ncbi.nlm.nih.gov/pubmed/19614892

An Endocannabinoid Signaling System Modulates Anxiety-like Behavior in Male Syrian Hamsters

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“An endocannabinoid signaling system has not been identified in hamsters.

We examined the existence of an endocannabinioid signaling system in Syrian hamsters using neuroanatomical, biochemical and behavioral pharmacological approaches.

The distribution of cannabinoid receptors was mapped and membrane fatty-acid amide hydrolase (FAAH) activity and levels of fatty-acid amides were measured in hamster brain. The impact of cannabinoid CB1 receptor blockade and inhibition of FAAH was evaluated in the elevated plus maze, rota-rod test and models of unconditioned and conditioned social defeat.

Results

A characteristic heterogeneous distribution of cannabinoid receptors was detected in hamster brain..

Endocannabinoids engage functional CB1 receptors in hamster brain to suppress anxiety-like behavior and undergo enzymatic hydrolysis catalyzed by FAAH. Our results further suggest that neither unconditioned nor conditioned social defeat in the Syrian hamster is dependent upon cannabinoid CB1 receptor activation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694060/

Effects of cannabinoids on the anxiety-like response in mice.

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“Several pieces of anatomical, biochemical and pharmacological evidence indicate that the endocannabinoid system via CB1 receptors is implicated in the control of emotional behavior. However, previous studies have reported unclear and contradictory results concerning the role of cannabinoids in anxiety. The aim of the present study was to examine the influence of the cannabinoid agonist WIN 55,212-2, the CB1 antagonist AM 281, the inhibitor of anandamide hydrolysis AACOCF3  and the inhibitor of anandamide transporter AM404 on the anxiety-like response in mice in the light/dark box test…

  These results support the hypothesis that the endocannabinoid system is involved in the regulation of anxiety-like behavior, and also suggest that the inhibitors of anandamide hydrolysis might be potential anxiolytic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/16702621

Facilitation of endocannabinoid effects in the ventral hippocampus modulates anxiety-like behaviors depending on previous stress experience.

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“Although several pieces of evidence indicate that the endocannabinoid system modulates anxiety-like behaviors and stress adaptation, few studies have investigated the brain sites of these effects. The ventral hippocampus (VHC) has been related to anxiety behaviors and has a high expression of cannabinoid-1 (CB1) receptors. Moreover, endocannabinoid signaling in the hippocampus is proposed to regulate stress adaptation. In the present study we investigated the role of previous stressful experience on the effects of AM404, an anandamide uptake inhibitor, microinjected into the VHC of rats submitted to the elevated plus maze (EPM), a widely used animal model of anxiety…

These results suggest that facilitation of endocannabinoid system neurotransmission in the ventral hippocampus modulates anxiety-like behaviors and that this effect depends on previous stress experience.”

http://www.ncbi.nlm.nih.gov/pubmed/20167262

The endocannabinoid and endovanilloid systems interact in the rat prelimbic medial prefrontal cortex to control anxiety-like behavior.

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“Cannabinoid receptor 1 (CB(1)) agonists usually induce dose-dependent biphasic effects on anxiety-related responses. Low doses induce anxiolytic-like effects, whereas high doses are ineffective or anxiogenic, probably due to activation of Transient Receptor Potential Vanilloid Type 1 (TRPV(1)) channels.

 In this study we have investigated this hypothesis by verifying the effects of the CB(1)/TRPV(1) agonist ACEA injected into the prelimbic medial prefrontal cortex (PL) and the participation of endocannabinoids in the anxiolytic-like responses induced by TRPV(1) antagonism, using the elevated plus-maze (EPM) and the Vogel conflict test (VCT). Moreover, we verified the expression of these receptors in the PL by double labeling immunofluorescence. ACEA induced anxiolytic-like effect in the intermediate dose, which was attenuated by previous injection of AM251, a CB(1) receptor antagonist. The higher and ineffective ACEA dose caused anxiogenic- and anxiolytic-like effects, when injected after AM251 or the TRPV(1) antagonist 6-iodonordihydrocapsaicin (6-I-CPS), respectively. Higher dose of 6-I-CPS induced anxiolytic-like effects both in the EPM and the VCT, which were prevented by previous administration of AM251. In addition, immunofluorescence showed that CB(1) and TRPV(1) receptors are closely located in the PL.

These results indicate that the endocannabinoid and endovanilloid systems interact in the PL to control anxiety-like behavior.”

http://www.ncbi.nlm.nih.gov/pubmed/22691536

Anxiolytic-like effects induced by blockade of transient receptor potential vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats.

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“The endocannabinoid anandamide, in addition to activating cannabinoid type 1 receptors (CB1), may act as an agonist at transient receptor potential vanilloid type 1 (TRPV1) channels. In the periaqueductal gray, CB1 activation inhibits, whereas TRPV1 increases, anxiety-like behavior. In the medial prefrontal cortex (mPFC), another brain region related to defensive responses, CB1 activation induces anxiolytic-like effects. However, a possible involvement of TRPV1 is still unclear.

In the present study, we tested the hypothesis that TRPV1 channel contributes to the modulation of anxiety-like behavior in the mPFC.

CONCLUSIONS:

These data suggest that TRPV1 in the ventral mPFC tonically inhibits anxiety-like behavior. TRPV1 could facilitate defensive responses opposing, therefore, the anxiolytic-like effects reported after local activation of CB1 receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/19387617

Anxiolytic-like effect induced by the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA), in the rat amygdala is mediated through the D1 and D2 dopaminergic systems.

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“In the present study the influence of the dopaminergic system(s) of the amygdala on the anxiolytic-like effect of the cannabinoid CB1 receptor agonist arachydonilcyclopropylamide (ACPA) in male Wistar rats was investigated. An elevated plus-maze test of anxiety was used to assess anxiety-like behaviors…

It can be concluded that the dopaminergic system of the amygdala may be involved, at least partly, in the anxiolytic-like effects induced by ACPA in the rat amygdala.”

http://www.ncbi.nlm.nih.gov/pubmed/20685770