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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.<\/jats:p>","DOI":"10.3390\/ijms24097709","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T04:01:23Z","timestamp":1682308883000},"page":"7709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phosphorylation of Neurofilament Light Chain in the VLO Is Correlated with Morphine-Induced Behavioral Sensitization in Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-4298","authenticated-orcid":false,"given":"Yu-Xiang","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Forensic Medicine, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"},{"name":"NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming 650032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Mei","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Forensic Medicine, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi-Xi","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Forensic Medicine, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei-Fei","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Forensic Medicine, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, 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Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Si","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Forensic Medicine, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Xia","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Forensic Medicine, Xi\u2019an Jiaotong University Health Science Center, Xi\u2019an 710061, China"},{"name":"The Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu-Quan","family":"Huo","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi\u2019an Jiaotong University, Xi\u2019an 710061, 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