title: Role of cannabinoid CB2 receptor in the reinforcing actions of ethanol.
abstract: This study examines the role of the cannabinoid CB2 receptor (CB2 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 CB2 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 (NAcc), respectively. CB2 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 CB2 KO mice presented increased μ-opioid receptor gene expression in NAcc. Acute ethanol administration (1-2 g/kg) increased TH and μ-opioid receptor gene expressions in CB2 KO mice, whereas the lower dose of ethanol decreased TH gene expression in WT mice. These results suggest that deletion of the CB2 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 CB2 r as a target for the treatment of problems related with alcohol consumption.
authors.affiliation: Unidad de Neuropsicofarmacología Traslacional, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ortega-Álvaro
authors.forename: Alexander
authors.initials: A
authors.lastname: Ternianov
authors.forename: Auxiliadora
authors.initials: A
authors.lastname: Aracil-Fernández
authors.forename: Francisco
authors.initials: F
authors.lastname: Navarrete
authors.forename: Maria Salud
authors.initials: MS
authors.lastname: García-Gutiérrez
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000235:genetics; D012054:Reinforcement, Psychology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000235:genetics; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D043885:Receptor, Cannabinoid, CB2; D017450:Receptors, Opioid, mu; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase
keywords: cannabinoid CB2 receptor; ethanol consumption; ethanol self-administration; knockout mice; tyrosine hydroxylase; μ-opioid receptor