title: CB1 cannabinoid receptor-mediated aggressive behavior.
abstract: This study examined the role of cannabinoid CB1 receptors (CB1r) in aggressive behavior. Social encounters took place in grouped and isolated mice lacking CB1r (CB1KO) and in wild-type (WT) littermates. Cognitive impulsivity was evaluated in the delayed reinforcement task (DRT). Gene expression analyses of monoaminooxidase-A (MAO-A), catechol-o-methyl-transferase (COMT), 5-hydroxytriptamine transporter (5-HTT) and 5-HT1B serotonergic receptor (5HT1Br) in the median and dorsal raphe nuclei (MnR and DR, respectively) and in the amygdala (AMY) were performed by real time-PCR. Double immunohistochemistry studies evaluated COMT and CB1r co-localization in the raphe nuclei and in the cortical (ACo), basomedian (BMA) and basolateral (BLA) amygdaloid nuclei. The behavioral effects of the CB1r agonist ACEA (1 and 2 mg/kg) on aggression were also evaluated in isolated OF1 mice. CB1KO mice housed in groups showed higher levels of offensive aggression. Isolation increased aggressive behavior only in WT. In grouped CB1KO mice COMT gene expression was significantly higher in the MnR and DR, while MAO-A gene expression was lower in the MnR. Gene expression of 5HT1Br, COMT and MAO-A was higher in the amygdala of CB1KO mice. CB1r double-immunohistochemistry revealed cytoplasmic-labeled COMT-ir cells in the raphe nuclei and in the ACo, BMA and BLA. CB1r immunolabeling was observed only in ACo, BMA and BLA, where it was localized in axons and buttons. The density of labeled processes increased in BLA. Acute administration of the CB1 agonist ACEA (2 mg/kg) significantly decreased the aggression levels of OF1 mice. These results suggest that CB1r plays an important role in social interaction and aggressive behavior.
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain; Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain. Electronic address: marta.rodriguez@uv.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodriguez-Arias
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain; Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Avda. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Navarrete
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain; Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Daza-Losada
authors.affiliation: Departamento de Histología, Universidad Miguel Hernández, 03550 San Juan de Alicante, Alicante, Spain.
authors.forename: Daniela
authors.initials: D
authors.lastname: Navarro
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain; Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Aguilar
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain; Departamento de Histología, Universidad Miguel Hernández, 03550 San Juan de Alicante, Alicante, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Berbel
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Avda. Blasco Ibáñez 21, 46010 Valencia, Spain; Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Miñarro
authors.affiliation: Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain; Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Avda. Ramón y Cajal s/n, 03550 San Juan de Alicante, Alicante, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Manzanares
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007175:Impulsive Behavior / Q000139:chemically induced; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000378:metabolism; D012054:Reinforcement, Psychology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D043884:Receptor, Cannabinoid, CB1; D044302:Receptor, Serotonin, 5-HT1B; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; C119325:arachidonyl-2-chloroethylamide; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase
keywords: ACEA; Aggression; CB1KO mice; Confocal microscopy; Gene expression; Social encounters