Transcriptome Sequencing Reveals Candidate NF-κB Target Genes Involved in Repeated Cocaine Administration

Abstract

BackgroundDrug-induced alterations in gene expression play an important role in the development of addictive behavior. Numerous transcription factors have been implicated in mediating the gene expression changes that occur in drug addiction. Nuclear factor kappa B is an inducible transcription factor complex that is rapidly activated by diverse stimuli.MethodsWe performed next-generation high-throughput sequencing of the prefrontal cortex in a mouse model of repeated cocaine administration combined with pharmacological nuclear factor kappa B inhibition to identify nuclear factor kappa B target genes that participate in the cocaine addiction process.ResultsWe found that the nuclear factor kappa B antagonist sodium diethyldithiocarbamate trihydrate significantly reversed the cocaine-induced expression changes of the amphetamine addiction pathway. Genes that demonstrated differential expression in response to cocaine treatment that was also reversed by sodium diethyldithiocarbamate trihydrate were enriched for the axon guidance pathway. Furthermore, the nuclear factor kappa B homo-dimer motif could be mapped to 86 of these sodium diethyldithiocarbamate trihydrate-reversed genes, which were also enriched for axon guidance.ConclusionsWe suggest that nuclear factor kappa B directly modifies the expression of axon guidance pathway members, leading to cocaine sensitization. Our findings reveal the role of prefrontal cortex nuclear factor kappa B activity in addiction and uncover the molecular mechanisms by which nuclear factor kappa B drives changes in the addicted brain.

Candidate l‐methionine target piRNA regulatory networks analysis response to cocaine‐conditioned place preference in mice

“…It showed that except Acyp2 gene, Cacna2d3, Epha6, Nedd4l and Vav2 were down‐regulated by MET via piRNA when induced by cocaine. And as for pathways these genes located such as mmu04024: cAMP signaling pathway, mmu04010: MAPK signaling pathway, mmu04360: Axon guidance and so on were reported related to drug dependence (Hope et al., 2007; Y. Wang et al., 2018).…”

Socioeconomic Burden of Psychiatric Cancer Patients: A Narrative Review

“…The socioeconomic challenges faced by people with addiction problems are complex and have significant consequences both for those affected and for society as a whole. Addiction, whether related to substances such as drugs and alcohol, activities such as gambling, or behaviors such as Internet or smartphone use, is considered a major public health problem with significant socioeconomic implications [ 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. The impact of addiction on an individual’s socioeconomic status manifests itself in various facets and includes economic hardship, homelessness, and incarceration [ 42 , 44 , 48 ].…”

“…The socioeconomic burden of addiction goes beyond the individual impact and extends to broader societal structures. For example, addiction causes significant damage to the health and socioeconomic positions of those affected, leading to additional burdens on society [ 43 , 47 ]. Furthermore, addiction is associated with increased healthcare costs, increased hospitalization, and unfavorable clinical outcomes, contributing to the overall socioeconomic impact [ 51 ].…”

Gene expression in the striatum of cynomolgus monkeys after chronic administration of cocaine and heroin

“…Chronic or repeated exposure to cocaine causes alterations in numerous genes in various regions of the brain in animal models 11,12 . In transcriptome profile analysis of the prefrontal cortex after repeated cocaine administration in mice, changes were identified in genes related to the MAPK signal pathway and NFκB target genes 13,14 . Some researchers have investigated the molecular effects of heroin addiction in animal models and human studies using microarrays 15‐17 .…”