Rivera, PatriciaBlanco, EduardoBindila, LauraAlen, FranciscoVargas, AntonioRubio, LeticiaPavón, Francisco JSerrano, AntoniaLutz, BeatRodríguez de Fonseca, FernandoSuárez, Juan2016-08-092016-08-092015-09-29Rivera P, Blanco E, Bindila L, Alen F, Vargas A, Rubio L, et al. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain. Front Cell Neurosci. 2015; 9:379http://hdl.handle.net/10668/2339Journal Article;Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.enAlcoholACEAJWH133CB1 receptorNeurogenesisCB2 receptorConsumo de alcoholAlcoholismoBenzamidasbromodesoxiuridinaCarbamatosGiro dentadoDietaEndocannabinoidesEtanolmarcadores genéticosHistonasHidrolasasHipotálamoVentrículos lateralesCélulas madre nerviosasNeuronasFosforilaciónRatasReceptor cannabinoide CB1SacarosaTubulina (proteína)Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol DrinkingMedical Subject Headings::Psychiatry and Psychology::Mental Disorders::Substance-Related Disorders::Alcohol-Related Disorders::AlcoholismMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::BenzamidesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::BromodeoxyuridineMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::CarbamatesMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate GyrusMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::DietMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::EndocannabinoidsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::EthanolMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic MarkersMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::HistonesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::HydrolasesMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::HypothalamusMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::Lateral VentriclesMedical Subject Headings::Anatomy::Cells::Stem Cells::Neural Stem CellsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::NeurogenesisMedical Subject Headings::Anatomy::Nervous System::NeuronsMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::PhosphorylationMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB2Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::SucroseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::TubulinMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Cannabinoid Receptor Modulators::Cannabinoid Receptor Agonistsresearch article26483633open access10.3389/fncel.2015.003791662-5102PMC4587308