Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats

• Published in: International journal of molecular sciences 2023-04, Vol.24 (9), p.7709
• Main Authors: Zhang, Yu-Xiang, Zhu, Yuan-Mei, Yang, Xi-Xi, Gao, Fei-Fei, Chen, Jie, Yu, Dong-Yu, Gao, Jing-Qi, Chen, Zhen-Nan, Yang, Jing-Si, Yan, Chun-Xia, Huo, Fu-Quan
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Brain; cAMP response element-binding protein (CREB); Chromatin; Cyclic AMP response element-binding protein; Drug addiction; Drug dosages; Epigenetics; extracellular signal-regulated kinase (ERK); Gene expression; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; histone deacetylases; Histone H3; Histones; Immunoprecipitation; Intermediate Filaments; Kinases; Learning; Lysine; Mental disorders; Microinjection; Morphine; Morphine - pharmacology; Narcotics; neurofilament light subunit (NF-L); Phenotypes; Phosphorylation; Proteins; Rats; Rats, Sprague-Dawley; Synapses; Trichostatin A; ventrolateral orbital cortex
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24097709

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.