Behavioral Evaluation of Seeking and Preference of Alcohol in Mice Subjected to Stress

Canseco-Alba, Ana; Schanz, Norman; Ishiguro, Hiroki; Liu, Qingrong; Onaivi, Emmanuel S.

doi:10.21769/bioprotoc.3061

Cited by 6 publications

(5 citation statements)

References 7 publications

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“…Control mice showed a significant enhanced preference in the CPP paradigm that was not present in DAT- CNR2 -/- mice. These results supported the idea that the absence of CB 2 r in dopaminergic neurons decreases alcohol consumption, even after acute stress, supporting the involvement of CB 2 r in alcohol dependence [ 71 ].…”

Section: Resultssupporting

confidence: 86%

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

García-Gutiérrez

Navarrete

Gasparyan

et al. 2022

IJMS

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Cumulative evidence has pointed out cannabinoid CB2 receptors (CB2r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB2r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles. The search strategy was as follows: “Receptor, Cannabinoid, CB2” AND “Alcohol-Related Disorders” AND “human/or patients”; “Receptor, Cannabinoid, CB2” AND “Alcohol” OR “Ethanol” AND “rodents/or mice/or rats”. Pharmacological approaches demonstrated that the activation or blockade of CB2r modulated different alcohol-addictive behaviors. Rodent models of alcoholism revealed significant alterations of CB2r in brain areas of the reward system. In addition, mice lacking CB2r (CB2KO) show increased alcohol consumption, motivation, and relapse alterations. It has been stressed that the potential neurobiological mechanisms underlying their behavioral effects involve critical elements of the alcohol reward system. Interestingly, recent postmortem studies showed CB2r gene expression alterations in brain areas of alcoholic patients. Moreover, although the number of studies is limited, the results revealed an association between some genetic alterations of the CB2r gene and an increased risk for developing AUD. This review provides evidence that CB2r may play a role in alcohol addiction. Clinical studies are necessary to figure out whether CB2r ligands may prove useful for the treatment of AUD in humans.

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Section: Resultssupporting

confidence: 86%

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

García-Gutiérrez

Navarrete

Gasparyan

et al. 2022

IJMS

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“…Contrary to this long-standing notion that the characteristic profile of catalepsy, hypothermia, antinociception, and hypomobility was mainly by CB1R agonism, our data using the Cre-loxP technology to generate mice with cell-specific deletion of CB2Rs in dopamine neurons and microglia reveals that CB2Rs are involved in the tetrad effects. We compared changes of the main effects of drugs and genotypes in DAT-Cnr2 Δ mice previously reported in our labs [ 2 , 49 ] and the main effects of drugs and genotypes in Cx3cr1-Cnr2 Δ mice by two-way ANOVA ( Table 1 ). Parallel results showed hyper-locomotor activity phenotype of the DAT-Cnr2 Δ mice in vehicle-treated but disappeared in CB1R and CB2R agonists-treated mice ( Figure 5 A).…”

Section: Resultsmentioning

confidence: 99%

“…The ratio of alcohol to water consumed, and the total fluid consumption was calculated to obtain a conditioned placement preference (CPP) ratio. These routine behavioral assays have been described elsewhere [ 2 , 40 , 49 ]. The animal experiments were performed in the laboratory of Professor Emmanuel Onaivi at William Paterson University in NJ.…”

Section: Methodsmentioning

confidence: 99%

Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

Liu

Canseco-Alba

Liang

et al. 2020

IJMS

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There are two well-characterized cannabinoid receptors (CB1R and CB2R and other candidates): the central nervous system (CNS) enriched CB1R and peripheral tissue enriched CB2R with a wide dynamic range of expression levels in different cell types of human tissues. Hepatocytes and neurons express low baseline CB1R and CB2R, respectively, and their cell-type-specific functions are not well defined. Here we report inducible expression of CB1R in the liver by high-fat and high sugar diet and CB2R in cortical neurons by methamphetamine. While there is less controversy about hepatocyte CB1R, the presence of functional neuronal CB2R is still debated to date. We found that neuron CB2R basal expression was higher than that of hepatocyte CB1R by measuring mRNA levels of specific isoform CB2A in neurons isolated by fluorescence-activated cell sorting (FACS) and CB1A in hepatocytes isolated by collagenase perfusion of liver. For in vivo studies, we generated hepatocyte, dopaminergic neuron, and microglia-specific conditional knockout mice (Abl-Cnr1Δ, Dat-Cnr2Δ, and Cx3cr1-Cnr2Δ) of CB1R and CB2R by crossing Cnr1f/f and Cnr2f/f strains to Abl-Cre, Dat-Cre, and Cx3cr1-Cre deleter mouse strains, respectively. Our data reveals that neuron and microglia CB2Rs are involved in the “tetrad” effects of the mixed agonist WIN 55212-2, CB1R selective agonist arachidonyl-2′-chloroethylamide (ACEA), and CB2R selective agonist JWH133. Dat-Cnr2Δ and Cx3cr1-Cnr2Δ mice showed genotypic differences in hypomobility, hypothermia, analgesia, and catalepsy induced by the synthetic cannabinoids. Alcohol conditioned place preference was abolished in DAT-Cnr2Δ mice and remained intact in Cx3cr1-Cnr2Δ mice in comparison to WT mice. These Cre-loxP recombinant mouse lines provide unique approaches in cannabinoid research for dissecting the complex endocannabinoid system that is implicated in many chronic disorders.

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“…A conditional knockout mouse was recently generated in which CNR2 expression was explicitly knocked down in DAT-Cnr2-/- dopaminergic neurons [ 77 ]. This was achieved using a recombinant expression system (Cre-LoxP) that utilized the dopamine transporter (DAT) promoter, producing DAT-Cnr2-/- mice.…”

Section: Therapeutic Potential Of Cb2r In the Management Of Substance Use Disordersmentioning

confidence: 99%

CB2 Receptor Involvement in the Treatment of Substance Use Disorders

García-Gutiérrez

Gasparyan

Navarro³

et al. 2021

Biomolecules

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The pharmacological modulation of the cannabinoid receptor 2 (CB2r) has emerged as a promising potential therapeutic option in addiction. The purpose of this review was to determine the functional involvement of CB2r in the effects produced by drugs of abuse at the central nervous system (CNS) level by assessing evidence from preclinical and clinical studies. In rodents, several reports suggest the functional involvement of CB2r in the effects produced by drugs of abuse such as alcohol, cocaine, or nicotine. In addition, the discovery of CB2r in brain areas that are part of the reward system supports the relevance of CB2r in the field of addiction. Interestingly, animal studies support that the CB2r regulates anxiety and depression behavioral traits. Due to its frequent comorbidity with neuropsychiatric disorders, these pharmacological actions may be of great interest in managing SUD. Preliminary clinical trials are focused on exploring the therapeutic potential of modulating CB2r in treating addictive disorders. These promising results support the development of new pharmacological tools regulating the CB2r that may help to increase the therapeutic success in the management of SUD.

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Behavioral Evaluation of Seeking and Preference of Alcohol in Mice Subjected to Stress

Cited by 6 publications

References 7 publications

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

CB2 Receptor Involvement in the Treatment of Substance Use Disorders

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