The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice

Mansouri, Shamma Al; Ojha, Shreesh; Maamari, Elyazia Al; Ameri, Mouza Al; Nurulain, Syed M.; Bahí, Amine

doi:10.1016/j.pbb.2014.06.025

Cited by 111 publications

(90 citation statements)

References 43 publications

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“…Transgenic mice with overexpression of CB 2 R in the brain show decreased cocaine self-administration and cocaine-enhanced 4 locomotion (Aracil-Fernandez et al, 2012). In addition, systemic administration of the CB 2 R agonist β-caryophyllene reduced voluntary alcohol intake, alcohol-induced condition place preference and locomotor sensitization in mice (Al Mansouri et al, 2014).…”

Section: Introductionmentioning

confidence: 94%

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

Zhang

et al. 2014

Neuropsychopharmacol

114

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: 94%

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

Zhang

et al. 2014

Neuropsychopharmacol

114

134

View full text Add to dashboard Cite

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“…Voluntary ethanol consumption and preference occurred under the two-bottle, free-choice paradigm, as previously described [29,36,40,41,[46][47][48][49][50][51][52][53]. In brief, the two 10 mL pipettes, one containing tap water and the other containing increasing concentrations of ethanol (2.5, 5, 10, 15 and 20%; v/v), were presented for 24 h/day for 5 consecutive days and their positions (left/right) were interchanged daily to prevent development of side preference.…”

Section: Two-bottle Choice Drinking Testmentioning

confidence: 99%

“…To determine the effect of OxtR overexpression on ethanol-induced hypnotic responses we used the LORR test as we have described previously in mice [51]. In brief, mice were administered a hypnotic dose of ethanol (3.5 g/kg, i.p.)…”

Section: Loss Of Righting Reflex (Lorr) Testmentioning

confidence: 99%

Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice

Bahí

Mansouri

Maamari

2016

Physiology & Behavior

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“…BCP has been reported to exert protective effects in experimental animal models of inflammatory pain (Gertsch et al, 2008), kidney injury (Horvath et al, 2012b), ischaemic stroke (Choi et al, 2013), Parkinson's disease (Ojha et al, 2016), toxic hepatitis (D-galactosamine-and endotoxin-induced) (Cho et al, 2015), experimental liver fibrosis (Mahmoud et al, 2014) and colitis (Bento et al, 2011). BCP has been also proposed recently, to have anti-addictive potential (Al Mansouri et al, 2014). BCP has been reported to act on targets other than CB 2 receptors, including sirtuin 1 (SIRT-1; Zheng et al, 2013), PPAR-α (Wu et al, 2014), fatty acid amide hydrolase (FAAH) or COX-2 (Chicca et al, 2014).…”

mentioning

confidence: 99%

β‐Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice

Varga

Mátyás

Erdélyi

et al. 2017

British J Pharmacology

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BACKGROUND AND AIMSβ-Caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo are reported to involve activation of cannabinoid CB 2 receptors that are predominantly expressed in immune cells. Here, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury. METHODSIn this study, we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS. RESULTSChronic treatment with BCP alleviated the chronic and binge alcohol-induced liver injury and inflammation by attenuating the pro-inflammatory phenotypic`M1`switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules intercellular adhesion molecule 1, E-Selectin and P-Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation and PPAR-α signalling). These protective effects of BCP against alcohol-induced liver injury were attenuated in CB 2 receptor knockout mice, indicating that the beneficial effects of this natural product in liver injury involve activation of these receptors. Following acute or chronic administration, BCP was detectable both in the serum and liver tissue homogenates but not in the brain. CONCLUSIONSGiven the safety of BCP in humans, this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.

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The cannabinoid receptor 2 agonist, β-caryophyllene, reduced voluntary alcohol intake and attenuated ethanol-induced place preference and sensitivity in mice

Cited by 111 publications

References 43 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

Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice

β‐Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice

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