Abstract:
The endocannabinoid system has been shown to be a powerful mediator of anxiety, learning and memory, as well as nociception behaviors. Exogenous cannabinoids like delta-9-tetrahydrocannabinol mimic the naturally occurring endogenous cannabinoids found in the mammalian central and peripheral nervous system. The hydrophobic properties of endocannabinoids mean that these psychoactive compounds require help with cellular transport. A family of lipid intracellular carriers called fatty acid-binding proteins (FABPs) can bind to endocannabinoids. Pharmacological inhibition or genetic deletion of FABP subtypes 5 and 7 elevates whole-brain anandamide (AEA) levels, a type of endocannabinoid. This study examined locomotor behavior, anxiety-like behavior, and social behavior in FABP5-/- and FABP7-/- mice. Furthermore, we measured N-methyl-D-aspartate (NMDA) receptor levels in the brain to help identify potential underlying mechanisms related to the behavioral findings. Results showed that both male and female FABP5-/- mice exhibited significantly lower activity when compared with both FABP5/7+/+ (control) and FABP7-/-. For social behavior, male, but not female, FABP5-/- mice spent more time interacting with novel mice compared with controls (FABP5/7+/+) and FABP7-/- mice. No significant difference was found for anxiety-like behavior. Results from the NMDA autoradiography revealed [3H] MK-801 binding to be significantly increased within sub-regions of the striatum in FABP7-/- compared with control. In summary, these results show that FABP5 deficiency plays a significant role in locomotion activity, exploratory behavior, as well as social interaction. Furthermore, FABP7 deficiency is shown to play an important role in NMDA receptor expression, while FABP5 does not.
摘要:
内源性大麻素系统已被证明是焦虑的强大媒介,学习和记忆,以及伤害性行为。如δ-9-四氢大麻酚的外源性大麻素模拟在哺乳动物中枢和外周神经系统中发现的天然存在的内源性大麻素。内源性大麻素的疏水特性意味着这些精神活性化合物需要细胞转运的帮助。称为脂肪酸结合蛋白(FABP)的脂质细胞内载体家族可以与内源性大麻素结合。FABP亚型5和7的药理学抑制或遗传缺失可提高全脑anandamide(AEA)水平,一种内源性大麻素。这项研究检查了运动行为,类似焦虑的行为,FABP5-/-和FABP7-/-小鼠的社会行为。此外,我们测量了大脑中N-甲基-D-天冬氨酸(NMDA)受体水平,以帮助确定与行为发现相关的潜在潜在机制.结果显示,与FABP5/7+/+(对照)和FABP7-/-小鼠相比,雄性和雌性FABP5-/-小鼠均表现出显著较低的活性。对于社会行为,男性,但不是女性,与对照(FABP5/7+/+)和FABP7-/-小鼠相比,FABP5-/-小鼠花费更多的时间与新型小鼠相互作用。焦虑样行为没有发现显着差异。NMDA放射自显影的结果表明,与对照组相比,FABP7-/-中[3H]MK-801的结合在纹状体的亚区域内显着增加。总之,这些结果表明,FABP5缺乏在运动活动中起着重要作用,探索行为,以及社交互动。此外,FABP7缺乏在NMDA受体表达中起重要作用,而FABP5没有。