Ten-Blanco Marc, Pereda-Pérez Inmaculada, Izquierdo-Luengo Cristina, Berrendero Fernando
Faculty of Experimental Sciences, Universidad Francisco de Vitoria, Madrid, Spain.
Front Pharmacol. 2022 Aug 23;13:975020. doi: 10.3389/fphar.2022.975020. eCollection 2022.
Genetic and environmental factors are implicated in the etiology of neuropsychiatric diseases. Inbred mouse strains, including the 129S1/SvImJ (S1), constitute important models to study the influence of genetic factors in these conditions. S1 mice displayed anxiogenic-like behavior, impaired fear extinction, and increased prepulse inhibition (PPI) of startle reflex compared to C57BL/6J (BL6) mice. Given the role played by the endocannabinoid system (ECS) in these responses, we evaluated the expression of the ECS components in different brain regions in S1 mice. Gene expression levels of the cannabinoid type-1 and type-2 receptors (CB1R and CB2R) and the endocannabinoid metabolizing enzymes varied depending on the brain region evaluated. Notably, CB2R expression markedly increased in the amygdala, prefrontal cortex and hippocampus in S1 mice. Moreover, CB2R blockade with SR144528 partially rescued the anxiogenic phenotype in S1 mice, while CB2R activation with JWH133 potentiated the deficits in fear extinction and the PPI of startle reflex in this mouse strain. These data suggest that CB2R is involved in the behavioral alterations observed in S1 mice and underline the importance of this cannabinoid receptor subtype in the regulation of certain central nervous system disorders.
遗传和环境因素与神经精神疾病的病因有关。近交系小鼠，包括129S1/SvImJ（S1），是研究遗传因素在这些疾病中影响的重要模型。与C57BL/6J（BL6）小鼠相比，S1小鼠表现出类似焦虑的行为、恐惧消退受损以及惊吓反射的前脉冲抑制（PPI）增加。鉴于内源性大麻素系统（ECS）在这些反应中所起的作用，我们评估了S1小鼠不同脑区中ECS成分的表达。1型和2型大麻素受体（CB1R和CB2R）以及内源性大麻素代谢酶的基因表达水平因所评估的脑区而异。值得注意的是，S1小鼠杏仁核、前额叶皮质和海马体中的CB2R表达明显增加。此外，用SR144528阻断CB2R可部分挽救S1小鼠的焦虑表型，而用JWH133激活CB2R则会加剧该小鼠品系的恐惧消退缺陷和惊吓反射的PPI。这些数据表明CB2R参与了S1小鼠中观察到的行为改变，并强调了这种大麻素受体亚型在调节某些中枢神经系统疾病中的重要性。
