A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands

Ishiguro, Hiroki; Carpio, O.; Horiuchi, Yasue; Shu, A.; Higuchi, Susumu; Schanz, Norman; Benno, Robert H.; Arinami, Tadao; Onaivi, Emmanuel S.

doi:10.1002/syn.20714

Cited by 57 publications

(55 citation statements)

References 33 publications

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“…Several independent groups have demonstrated a functional role for brain CB 2 Rs in terms of genetic association with psychiatric diseases (Ishiguro et al, 2010a;Ishiguro et al, 2010b), cellular distributions and neuronal localizations (Lanciego et al, 2011;Suarez et al, 2009;Van Sickle et al, 2005), electrophysiological effects (den Boon et al, 2012;Morgan et al, 2009), and behavioral pharmacological effects using CB 2 R transgenic mice (Callen et al, 2012;Garcia-Gutierrez and Manzanares, 2011;Garcia-Gutierrez et al, 2013;Navarrete et al, 2013;Xi et al, 2011). Strikingly, growing evidence demonstrates that brain CB 2 Rs may be involved in drug reward and addiction.…”

Section: Introductionmentioning

confidence: 96%

Species Differences in Cannabinoid Receptor 2 and Receptor Responses to Cocaine Self-Administration in Mice and Rats

Zhang

et al. 2014

Neuropsychopharmacol

112

134

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The discovery of functional cannabinoid receptors 2 (CB2Rs) in brain suggests a potential new therapeutic target for neurological and psychiatric disorders. However, recent findings in experimental animals appear controversial. Here we report that there are significant species differences in CB2R mRNA splicing and expression, protein sequences, and receptor responses to CB2R ligands in mice and rats. Systemic administration of JWH133, a highly selective CB2R agonist, significantly and dose-dependently inhibited intravenous cocaine self-administration under a fixed ratio (FR) schedule of reinforcement in mice, but not in rats. However, under a progressive ratio (PR) schedule of reinforcement, JWH133 significantly increased breakpoint for cocaine self-administration in rats, but decreased it in mice. To explore the possible reasons for these conflicting findings, we examined CB2R gene expression and receptor structure in the brain. We found novel rat-specific CB2C and CB2D mRNA isoforms in addition to CB2A and CB2B mRNA isoforms. In situ hybridization RNAscope assays found higher levels of CB2R mRNA in different brain regions and cell types in mice than in rats. By comparing CB2R-encoding regions, we observed a premature stop codon in the mouse CB2R gene that truncated 13 amino-acid residues including a functional autophosphorylation site in the intracellular C-terminus. These findings suggest that species differences in the splicing and expression of CB2R genes and receptor structures may in part explain the different effects of CB2R-selective ligands on cocaine self-administration in mice and rats.

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Section: Introductionmentioning

confidence: 96%

Species Differences in Cannabinoid Receptor 2 and Receptor Responses to Cocaine Self-Administration in Mice and Rats

Zhang

et al. 2014

Neuropsychopharmacol

112

134

View full text Add to dashboard Cite

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“…A common CB2 variant, Q63R, causing reduced CB2 function, has been associated with eating disorders in humans (20). CB2 agonists reduce food intake in lean mice (20) and improve both body weight and obesity-associated inflammation in diet-induced obese mice (21).…”

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confidence: 99%

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Rossi¹,

Bellini

Luongo

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…However, in recent years, potential involvement of the CB 2 receptor in drug addiction has been revealed [112][113][114][115][116][117]. Three studies have evaluated the role of CB 2 receptor in mediating nicotine reward.…”

Section: Role Of Cb 2 Receptors In Nicotine Addictionmentioning

confidence: 98%

Cannabinoid-Nicotine Interactions

Auber

Justinová

Scherma

et al. 2015

Cannabinoid Modulation of Emotion, Memory, and Motivation

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Although nicotine and delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredients in tobacco and cannabis, bind to different receptors in the brain, they have several features in common. Each of these drugs is typically selfadministered by smoking, and this behavior is maintained by rewarding effects that are mediated by brain circuitry that at least partially overlaps between the drugs. Each tends to be used chronically, leading to dependence and addiction in many users. Perhaps most importantly, the nicotinic and cannabinergic systems appear to interact in such a way that modulating one system can enhance or counteract effects of the other system. Therefore, studying cannabinoid-nicotine interactions could potentially lead to new treatments for addiction. This chapter considers such interactions, focusing on recent preclinical work that suggests manipulating the cannabinoid system can counteract the addictive effects of nicotine that manipulating the nicotinic system can counteract the addictive effects of cannabis, and that prior or concurrent use of cannabis has the detrimental effect of increasing the addictive effects of nicotine. Interactive effects of these systems on anxiety and memory are also considered, although these have been studied less than addiction-related effects.

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A nonsynonymous polymorphism in cannabinoid CB2 receptor gene is associated with eating disorders in humans and food intake is modified in mice by its ligands

Cited by 57 publications

References 33 publications

Species Differences in Cannabinoid Receptor 2 and Receptor Responses to Cocaine Self-Administration in Mice and Rats

Species Differences in Cannabinoid Receptor 2 and Receptor Responses to Cocaine Self-Administration in Mice and Rats

Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation

Cannabinoid-Nicotine Interactions

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