scholarly journals Obesity as a Condition Determined by Food Addiction: Should Brain Endocannabinoid System Alterations Be the Cause and Its Modulation the Solution?

2021 ◽  
Vol 14 (10) ◽  
pp. 1002
Author(s):  
Marialuisa de Ceglia ◽  
Juan Decara ◽  
Silvana Gaetani ◽  
Fernando Rodríguez de Fonseca
Keyword(s):  
Cannabinoid Receptors ◽  
Food Addiction ◽  
Endocannabinoid System ◽  
Reward System ◽  
Brain Regions ◽  
Pharmacological Therapy ◽  
Behavioral Disorder ◽  
Complex Disorder ◽  
Mood Effects ◽  
Determining Factor

Obesity is a complex disorder, and the number of people affected is growing every day. In recent years, research has confirmed the hypothesis that food addiction is a determining factor in obesity. Food addiction is a behavioral disorder characterized by disruptions in the reward system in response to hedonic eating. The endocannabinoid system (ECS) plays an important role in the central and peripheral control of food intake and reward-related behaviors. Moreover, both obesity and food addiction have been linked to impairments in the ECS function in various brain regions integrating peripheral metabolic signals and modulating appetite. For these reasons, targeting the ECS could be a valid pharmacological therapy for these pathologies. However, targeting the cannabinoid receptors with inverse agonists failed when used in clinical contexts as a consequence of the induction of affective disorders. In this context, new classes of drugs acting either on CB1 and/or CB2 receptors or on synthetic and degradation enzymes of endogenous cannabinoids are being studied. However, further investigation is necessary to find safe and effective treatments that can exert anti-obesity effects, normalizing reward-related behaviors without causing important adverse mood effects.

scholarly journals Distribution of the Cannabinoid Receptor Type 1 in the Brain of the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

2021 ◽  
Vol 15 ◽  
Author(s):  
Alejando Fuerte-Hortigón ◽  
Jaime Gonçalves ◽  
Laura Zeballos ◽  
Rubén Masa ◽  
Ricardo Gómez-Nieto ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Audiogenic Seizure ◽  
Type I ◽  
Sound Stimulation ◽  
Differential Distribution ◽  
Central Type ◽  
Anatomical Basis

The endocannabinoid system modulates epileptic seizures by regulating neuronal excitability. It has become clear that agonist activation of central type I cannabinoid receptors (CB1R) reduces epileptogenesis in pre-clinical animal models of epilepsy. The audiogenic seizure-prone hamster GASH/Sal is a reliable experimental model of generalized tonic-clonic seizures in response to intense sound stimulation. However, no studies hitherto had investigated CB1R in the GASH/Sal. Although the distribution of CB1R has been extensively studied in mammalian brains, their distribution in the Syrian golden hamster brain also remains unknown. The objective of this research is to determine by immunohistochemistry the differential distribution of CB1R in the brains of GASH/Sal animals under seizure-free conditions, by comparing the results with wild-type Syrian hamsters as controls. CB1R in the GASH/Sal showed a wide distribution in many nuclei of the central nervous system. These patterns of CB1R-immunolabeling are practically identical between the GASH/Sal model and control animals, varying in the intensity of immunostaining in certain regions, being slightly weaker in the GASH/Sal than in the control, mainly in brain regions associated with epileptic networks. The RT-qPCR analysis confirms these results. In summary, our study provides an anatomical basis for further investigating CB1R in acute and kindling audiogenic seizure protocols in the GASH/Sal model as well as exploring CB1R activation via exogenously administered cannabinoid compounds.

Endocannabinoid-Mediated Control of Synaptic Transmission

2009 ◽  
Vol 89 (1) ◽  
pp. 309-380 ◽  
Author(s):  
Masanobu Kano ◽  
Takako Ohno-Shosaku ◽  
Yuki Hashimotodani ◽  
Motokazu Uchigashima ◽  
Masahiko Watanabe
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Signaling ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
New Era ◽  
Behavioral Studies ◽  
Electrophysiological Studies ◽  
The Brain ◽  
Subsequent Identification

The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB1 receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.

scholarly journals Role of Cannabinoid Receptors in Psychological Disorder

2020 ◽  
Vol 3 (4) ◽  
pp. 199-208
Author(s):  
Ambika Nand Jha ◽  
Dhaval M Patel
Keyword(s):  
Cannabinoid Receptors ◽  
Biological Effects ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
The Body ◽  
Psychological Disorder ◽  
Physiological Processes ◽  
Neurochemical Changes ◽  
G Protein Coupled

Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system. Cannabinoid CB1 and CB2 receptors are G protein-coupled receptors present from the early stages of gestation, which is involved in various physiological processes, including appetite, pain-sensation, mood, and memory. Due to the lipophilic nature of cannabinoids, it was initially thought that these compounds exert several biological effects by disrupting the cell membrane nonspecifically. Recent biochemical and behavioral findings have demonstrated that blockade of CB1 receptors engenders antidepressant-like neurochemical changes (increases in extracellular levels of monoamines in cortical but not subcortical brain regions) and behavioral effects consistent with antidepressant/antistress activity. We aim to define various roles of cannabinoid receptors in modulating signaling pathways and association with several pathophysiological conditions.

scholarly journals Inherent Sex Differences in the Expression of the Endocannabinoid System within V1M Cortex and PAG of Sprague Dawley Rats

2021 ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background: Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system is comprised of the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods: Brain tissue from naïve male and female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unbiased proteomic analysis, and immunohistochemistry. Results: Mass spectrometry revealed cortical AEA levels were significantly higher in males compared to females (p<0.001), whereas 2-AG levels in periaqueductal grey were significantly higher in females compared to males (p<0.0001). Immunohistochemistry followed by unbiased proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG.Conclusions: Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

scholarly journals Sex differences in the expression of the endocannabinoid system within V1M cortex and PAG of Sprague Dawley rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A. Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented, but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system comprises the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods Brain tissue from naïve male and estrous staged female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unlabeled quantitative proteomic analysis, and immunohistochemistry. Results Mass spectrometry revealed significant differences in 2-AG and AEA concentrations between males and females, as well as between female estrous cycle stages. Specifically, 2-AG concentration was lower within female PAG as compared to male PAG (*p = 0.0077); female 2-AG concentration within the PAG did not demonstrate estrous stage dependence. Immunohistochemistry followed by proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG. Conclusions Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

scholarly journals Cocaine-Induced Reinstatement of Cocaine Seeking Provokes Changes in the Endocannabinoid and N-Acylethanolamine Levels in Rat Brain Structures

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1125 ◽  
Author(s):  
Beata Bystrowska ◽  
Małgorzata Frankowska ◽  
Irena Smaga ◽  
Ewa Niedzielska-Andres ◽  
Lucyna Pomierny-Chamioło ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Rat Brain ◽  
Cannabinoid Receptors ◽  
Strong Support ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Priming Dose ◽  
Self Administration ◽  
Drug Induced

There is strong support for the role of the endocannabinoid system and the noncannabinoid lipid signaling molecules, N-acylethanolamines (NAEs), in cocaine reward and withdrawal. In the latest study, we investigated the changes in the levels of the above molecules and expression of cannabinoid receptors (CB1 and CB2) in several brain regions during cocaine-induced reinstatement in rats. By using intravenous cocaine self-administration and extinction procedures linked with yoked triad controls, we found that a priming dose of cocaine (10 mg/kg, i.p.) evoked an increase of the anadamide (AEA) level in the hippocampus and prefrontal cortex only in animals that had previously self-administered cocaine. In the same animals, the level of 2-arachidonoylglycerol (2-AG) increased in the hippocampus and nucleus accumbens. Moreover, the drug-induced relapse resulted in a potent increase in NAEs levels in the cortical areas and striatum and, at the same time, a decrease in the tissue levels of oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) was noted in the nucleus accumbens, cerebellum, and/or hippocampus. At the level of cannabinoid receptors, a priming dose of cocaine evoked either upregulation of the CB1 and CB2 receptors in the prefrontal cortex and lateral septal nuclei or downregulation of the CB1 receptors in the ventral tegmental area. In the medial globus pallidus we observed the upregulation of the CB2 receptor only after yoked chronic cocaine treatment. Our findings support that in the rat brain, the endocannabinoid system and NAEs are involved in cocaine induced-reinstatement where these molecules changed in a region-specific manner and may represent brain molecular signatures for the development of new treatments for cocaine addiction.

scholarly journals Endocannabinoid system and pain: an introduction

2013 ◽  
Vol 73 (1) ◽  
pp. 106-117 ◽  
Author(s):  
James J. Burston ◽  
Stephen G. Woodhams
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Clinical Work ◽  
Brain Regions ◽  
Ventrolateral Medulla ◽  
Cannabinoid Type 1 Receptor ◽  
Pain Pathway

The endocannabinoid (EC) system consists of two main receptors: cannabinoid type 1 receptor cannabinoid receptors are found in both the central nervous system (CNS) and periphery, whereas the cannabinoid type 2 receptor cannabinoid receptor is found principally in the immune system and to a lesser extent in the CNS. The EC family consists of two classes of well characterised ligands; the N-acyl ethanolamines, such as N-arachidonoyl ethanolamide or anandamide (AEA), and the monoacylglycerols, such as 2-arachidonoyl glycerol. The various synthetic and catabolic pathways for these enzymes have been (with the exception of AEA synthesis) elucidated. To date, much work has examined the role of EC in nociceptive processing and the potential of targeting the EC system to produce analgesia. Cannabinoid receptors and ligands are found at almost every level of the pain pathway from peripheral sites, such as peripheral nerves and immune cells, to central integration sites such as the spinal cord, and higher brain regions such as the periaqueductal grey and the rostral ventrolateral medulla associated with descending control of pain. EC have been shown to induce analgesia in preclinical models of acute nociception and chronic pain states. The purpose of this review is to critically evaluate the evidence for the role of EC in the pain pathway and the therapeutic potential of EC to produce analgesia. We also review the present clinical work conducted with EC, and examine whether targeting the EC system might offer a novel target for analgesics, and also potentially disease-modifying interventions for pathophysiological pain states.

scholarly journals Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1845
Author(s):  
Stephen Schultz ◽  
Georgianna G. Gould ◽  
Nicola Antonucci ◽  
Anna Lisa Brigida ◽  
Dario Siniscalco
Keyword(s):  
Autism Spectrum Disorder ◽  
Cannabinoid Receptors ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Blood Levels ◽  
Increased Risk ◽  
Patterns Of Behavior ◽  
Arachidonoyl Glycerol

Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.

scholarly journals Cannabinoid receptors distribution in mouse cortical plasma membrane compartments

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hajar Miranzadeh Mahabadi ◽  
Haseeb Bhatti ◽  
Robert B. Laprairie ◽  
Changiz Taghibiglou
Keyword(s):  
Plasma Membrane ◽  
Lipid Raft ◽  
Cannabinoid Receptors ◽  
Gradient Centrifugation ◽  
Brain Regions ◽  
Cb1 Receptor ◽  
The Body ◽  
Cb2 Receptor ◽  
Cortical Tissue ◽  
Ionic Detergent

AbstractThe type 1 and type 2 cannabinoid receptors (CB1 and CB2 receptors) are class A G protein-coupled receptors (GPCRs) that are activated by endogenous lipids called endocannabinoids to modulate neuronal excitability and synaptic transmission in neurons throughout the central nervous system (CNS), and inflammatory processes throughout the body. CB1 receptor is one of the most abundant GPCRs in the CNS and is involved in many physiological and pathophysiological processes, including mood, appetite, and nociception. CB2 receptor is primarily found on immunomodulatory cells of both the CNS and the peripheral immune system. In this study, we isolated lipid raft and non-lipid raft fractions of plasma membrane (PM) from mouse cortical tissue by using cold non-ionic detergent and sucrose gradient centrifugation to study the localization of CB1 receptor and CB2 receptor. Lipid raft and non-lipid raft fractions were confirmed by flotillin-1, caveolin-1 and transferrin receptor as their protein biomarkers. Both CB1 receptor and CB2 receptor were found in non-raft compartments that is inconsistent with previous findings in cultured cell lines. This study demonstrates compartmentalization of both CB1 receptor and CB2 receptor in cortical tissue and warrants further investigation of CB1 receptor and CB2 receptor compartmental distribution in various brain regions and cell types.

scholarly journals Pros and Cons of the Cannabinoid System in Cancer: Focus on Hematological Malignancies

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3866
Author(s):  
Natasha Irrera ◽  
Alessandra Bitto ◽  
Emanuela Sant’Antonio ◽  
Rita Lauro ◽  
Caterina Musolino ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Hematological Malignancies ◽  
Antitumor Agents ◽  
Control Cell ◽  
Experimental Studies ◽  
Endocannabinoid System ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Growth ◽  
Cell Functions ◽  
Novel Approach

The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.

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