Rodriguez-Arias Marta, Navarrete Francisco, Daza-Losada Manuel, Navarro Daniela, Aguilar María A, Berbel Pere, Miñarro José, Manzanares Jorge
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.
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.
Neuropharmacology. 2013 Dec;75:172-80. doi: 10.1016/j.neuropharm.2013.07.013. Epub 2013 Aug 2.
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.
本研究考察了大麻素CB1受体（CB1r）在攻击行为中的作用。社交互动发生在缺乏CB1r的群居和独居小鼠（CB1基因敲除小鼠，CB1KO）以及野生型（WT）同窝小鼠中。在延迟强化任务（DRT）中评估认知冲动性。通过实时聚合酶链反应对中缝核和背侧中缝核（分别为MnR和DR）以及杏仁核（AMY）中的单胺氧化酶A（MAO-A）、儿茶酚-O-甲基转移酶（COMT）、5-羟色胺转运体（5-HTT）和5-HT1B血清素能受体（5HT1Br）进行基因表达分析。双重免疫组织化学研究评估了COMT和CB1r在中缝核以及皮质杏仁核（ACo）、基底内侧杏仁核（BMA）和基底外侧杏仁核（BLA）中的共定位。还在独居的OF1小鼠中评估了CB1r激动剂ACEA（1和2mg/kg）对攻击行为的影响。群居的CB1KO小鼠表现出更高水平的攻击性攻击。隔离仅在WT小鼠中增加攻击行为。在群居的CB1KO小鼠中，MnR和DR中的COMT基因表达显著更高，而MnR中的MAO-A基因表达更低。CB1KO小鼠杏仁核中的5HT1Br、COMT和MAO-A基因表达更高。CB1r双重免疫组织化学显示中缝核以及ACo、BMA和BLA中有胞质标记的COMT免疫反应阳性细胞。仅在ACo、BMA和BLA中观察到CB1r免疫标记，其定位于轴突和纽扣。BLA中标记突起的密度增加。急性给予CB1激动剂ACEA（2mg/kg）显著降低了OF1小鼠的攻击水平。这些结果表明CB1r在社交互动和攻击行为中起重要作用。
