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

• Main Authors: Chen, J. (Author), Chen, Z.-N (Author), Gao, F.-F (Author), Gao, J.-Q (Author), Huo, F.-Q (Author), Yan, C.-X (Author), Yang, J.-S (Author), Yang, X.-X (Author), Yu, D.-Y (Author), Zhang, Y.-X (Author), Zhu, Y.-M (Author)
• Format: Article
• Language: English
• Published: MDPI 2023
• Subjects: animal; Animals; cAMP response element-binding protein (CREB); extracellular signal-regulated kinase (ERK); histone deacetylase inhibitor; Histone Deacetylase Inhibitors; histone deacetylases; intermediate filament; Intermediate Filaments; learning; Learning; morphine; Morphine; neurofilament light subunit (NF-L); phosphorylation; Phosphorylation; rat; Rats; Rats, Sprague-Dawley; Sprague Dawley rat; ventrolateral orbital cortex
• Online Access: View Fulltext in Publisher; View in Scopus

 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 NF-L 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. © 2023 by the authors.