Goulart Vanessa Gama, Rocha-Mendonça Henrique, Maisonnette Silvia, Pandolfo Pablo, Landeira-Fernandez J, Campello-Costa Paula
Federal Fluminense University, Biology Institute, Neuroscience Program, Niteroi, Brazil.
Federal University of Rio de Janeiro, Biophysics Institute, Rio de Janeiro, Brazil.
Mol Cell Neurosci. 2021 Oct;116:103666. doi: 10.1016/j.mcn.2021.103666. Epub 2021 Aug 28.
Anxiety is an emotional state that affects the quality of human life. Several neurotransmitters are involved in the regulation of anxiety, including glutamate. The major actions of glutamate are mediated by N-methyl-d-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The present study performed a behavioral and neurochemical analysis of Carioca High-conditioned Freezing (CHF) and Carioca Low-conditioned Freezing (CLF) rats compared with control rats. We evaluated thermal nociception, anxiety-like behavior, depressive-like behavior, spatial memory, habituation memory, and the content and localization of different glutamatergic receptor subunits and postsynaptic density-95 (PSD-95), a postsynaptic protein. The CHF group exhibited an anxious-like phenotype, impairments in habituation and spatial memory, and a depressive-like phenotype compared with the control group. In the ventral hippocampus, an increase in the PSD-95, GluN1 and GluA1 subunits and a decrease in the GluN2A subunit of glutamatergic receptors. The CLF group exhibited a less anxious-like phenotype, hyperlocomotion and habituation impairments. Also, CLF animals, presented, in the ventral hippocampus, an increase in the PSD-95, GluN1 and GluA2 subunits and a decrease in the GluN2B subunit. These results suggest that the differential composition of NMDAR and AMPAR subunits may be related to the modulation of different phenotypes in CHF and CLF rats, which may help identify new targets for therapeutic interventions for anxiety disorders and other comorbidities.
焦虑是一种影响人类生活质量的情绪状态。几种神经递质参与焦虑的调节，包括谷氨酸。谷氨酸的主要作用由N-甲基-D-天冬氨酸受体（NMDARs）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）介导。本研究对Carioca高条件性僵住（CHF）和Carioca低条件性僵住（CLF）大鼠与对照大鼠进行了行为和神经化学分析。我们评估了热痛觉、焦虑样行为、抑郁样行为、空间记忆、习惯化记忆，以及不同谷氨酸能受体亚基和突触后密度蛋白95（PSD-95，一种突触后蛋白）的含量和定位。与对照组相比，CHF组表现出焦虑样表型、习惯化和空间记忆受损以及抑郁样表型。在腹侧海马体中，突触后密度蛋白95、谷氨酸能受体亚基GluN1和GluA1增加，而谷氨酸能受体亚基GluN2A减少。CLF组表现出较少的焦虑样表型、运动亢进和习惯化受损。此外，CLF动物在腹侧海马体中，突触后密度蛋白95、GluN1和GluA2亚基增加，而GluN2B亚基减少。这些结果表明，NMDAR和AMPAR亚基的不同组成可能与CHF和CLF大鼠不同表型的调节有关，这可能有助于确定焦虑症和其他合并症治疗干预的新靶点。
