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Role of cannabinoid CB 2 receptor in the reinforcing actions of ethanol
Author(s) -
OrtegaÁlvaro Antonio,
Ternianov Alexander,
AracilFernández Auxiliadora,
Navarrete Francisco,
GarcíaGutiérrez Maria Salud,
Manzanares Jorge
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12076
Subject(s) - conditioned place preference , nucleus accumbens , ethanol , self administration , chemistry , cannabinoid , ventral tegmental area , opioid , cannabinoid receptor , opioid receptor , pharmacology , endocrinology , receptor , medicine , psychology , biochemistry , dopamine , antagonist , dopaminergic
Abstract This study examines the role of the cannabinoid CB 2 receptor ( CB 2 r ) on the vulnerability to ethanol consumption. The time‐related and dose‐response effects of ethanol on rectal temperature, handling‐induced convulsions ( HIC ) and blood ethanol concentrations were evaluated in CB 2 KO and wild‐type ( WT ) mice. The reinforcing properties of ethanol were evaluated in conditioned place preference ( CPP ), preference and voluntary ethanol consumption and oral ethanol self‐administration. Water‐maintained behavior schedule was performed to evaluate the degree of motivation induced by a natural stimulus. Preference for non‐alcohol tastants assay was performed to evaluate the differences in taste sensitivity. Tyrosine hydroxylase ( TH ) and μ‐opioid receptor gene expressions were also measured in the ventral tegmental area and nucleus accumbens ( NA cc), respectively. CB 2 KO mice presented increased HIC score, ethanol‐ CPP , voluntary ethanol consumption and preference, acquisition of ethanol self‐administration, and increased motivation to drink ethanol compared with WT mice. No differences were found between genotypes in the water‐maintained behavior schedule or preference for non‐alcohol tastants. Naïve CB 2 KO mice presented increased μ‐opioid receptor gene expression in NA cc. Acute ethanol administration (1–2 g/kg) increased TH and μ‐opioid receptor gene expressions in CB 2 KO mice, whereas the lower dose of ethanol decreased TH gene expression in WT mice. These results suggest that deletion of the CB 2 r gene increased preference for and vulnerability to ethanol consumption, at least in part, by increased ethanol‐induced sensitivity of the TH and μ‐opioid receptor gene expressions in mesolimbic neurons. Future studies will determine the role of CB 2 r as a target for the treatment of problems related with alcohol consumption.