Localization of the cannabinoid type‐1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus

Glia, Journal Year: 2018, Volume and Issue: 66(7), P. 1417 - 1431

Published: Feb. 26, 2018

Abstract Astroglial type‐1 cannabinoid (CB 1 ) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed pre‐ post‐synaptic neuronal elements surrounding astrocyte processes. However, little is known concerning subcellular distribution of astroglial CB receptors. In particular, brain mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence mitochondrial membranes. Whether present mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking receptor expression specifically glial fibrillary acidic protein (GFAP)‐containing astrocytes (GFAP‐ ‐KO mice) also generated genetic rescue to re‐express exclusively ‐RS). better identify structures immunoelectron microscopy, global ( ‐KO) wild‐type ‐WT) littermates were intra‐hippocampally injected an adeno‐associated virus expressing humanized renilla green fluorescent (hrGFP) under control human GFAP promoter generate GFAPhrGFP‐ ‐WT mice, respectively. Furthermore, double immunogold (for immunoperoxidase or hrGFP) revealed that from different hippocampal regions ‐WT, GFAP‐ ‐RS mice. Only non‐specific gold particles detected mouse hippocampi Altogether, demonstrated existence a precise molecular architecture will have be taken into account evaluating activity cannabinergic signaling synapse.

Language: Английский

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Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

Frontiers in Pharmacology, Journal Year: 2016, Volume and Issue: 7

Published: Nov. 8, 2016

There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While chronic use cannabis itself considered risk factor contributing schizophrenia, triggered by phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC), cannabidiol, second most important phytocannabinoid, appears have no psychotomimetic potential. Although results from animal studies are inconsistent certain extent seem depend on behavioral paradigms, treatment duration experimental conditions applied, cannabidiol shown properties rodents rhesus monkeys. After some individual attempts, first randomized, double-blind controlled clinical trial had conducted demonstrated that exerts acute schizophrenia comparable drug amisulpride accompanied superior, placebo-like side effect profile. As improvement was significantly associated with elevated anandamide levels, it likely its action based mechanisms increased concentrations. However, plethora suggested, but their relevance effects needs still be investigated. clarification these as well establishment cannabidiol's efficacy hopefully benign profile remains subject number previously started trials.

Language: Английский

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Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake

Proceedings of the National Academy of Sciences, Journal Year: 2017, Volume and Issue: 114(25)

Published: June 5, 2017

Significance Suitable chemical tools have been instrumental in the discovery and characterization of endocannabinoid system. However, lack potent selective inhibitors for transport has prevented molecular this process. Current uptake are poorly bioavailable to central nervous system (CNS) weakly because they also inhibit fatty acid amide hydrolase (FAAH), major anandamide-degrading enzyme. Few studies addressed inhibition 2-arachidonoyl glycerol (2-AG), which is endocannabinoid. Here, we report a highly reuptake inhibitor. Our data indicate that across membrane can be targeted, leading general antiinflammatory anxiolytic effects mice.

Language: Английский

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Cannabinoids and the endocannabinoid system in reward processing and addiction: from mechanisms to interventions

Dialogues in Clinical Neuroscience, Journal Year: 2020, Volume and Issue: 22(3), P. 241 - 250

Published: Sept. 30, 2020

The last decades have seen a major gain in understanding the action of cannabinoids and endocannabinoid system reward processing development addictive behavior. Cannabis-derived psychoactive compounds such as Δ9-tetrahydrocannabinol synthetic directly interact with thereby properties. Cannabinoids induce their reinforcing properties by an increase tonic dopamine levels through cannabinoid type 1 (CB1) receptor–dependent mechanism within ventral tegmental area. Cues that are conditioned to cannabis smoking can drug-seeking responses (ie, craving) eliciting phasic events. A dopamine-independent involved involves endocannabinoid/glutamate interaction corticostriatal part system. In conclusion, pharmacological blockade signaling should lead reduction drug craving subsequently reduce relapse behavior addicted individuals. Indeed, there is increasing preclinical evidence targeting reduces relapse, allosteric modulators at CB1 receptors fatty acid amide hydrolase inhibitors clinical for use disorder. Cannabidiol, which mainly acts on CB2 receptors, currently being tested patients alcohol disorder opioid

Language: Английский

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Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening

Neuron, Journal Year: 2020, Volume and Issue: 105(6), P. 1062 - 1076.e6

Published: Jan. 13, 2020

Language: Английский

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