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Learn MoreNicotine dependence is responsible for perpetuating the adverse health effects due to tobacco use, the leading cause of preventable death worldwide. Nicotine is an agonist for nicotinic acetylcholine receptors, which are enriched in the habenulo-interpeduncular withdrawal circuit. Drugs of abuse, including nicotine, induce stable neuroadaptations, requiring protein synthesis through regulation of transcription factors, epigenetic mechanisms, and non-coding RNAs. It also been shown that miRNAs in brain are regulated by nicotine and that miRNA dysregulation contributes to brain dysfunction, including drug addiction. While much is known about the neurocircuitry responsible for the behaviors associated with nicotine reward or withdrawal, the underlying mechanisms of how changes in behavior are induced are less clear. Using miRNA- and mRNA-Seq, we demonstrate that there are widespread changes in both miRNA and mRNA expression in the IPN and MHb during acute nicotine withdrawal. Conserved, differentially expressed miRNAs were predicted to target inversely regulated mRNAs. This dataset represents a valuable resource, identifying a multitude of miRNAs/genes, which upon further study may reveal new mechanisms underlying the neuroadaptations of nicotine dependence and the symptoms of nicotine withdrawal. SOURCE: Alper Kucukural (alper.kucukural@umassmed.edu) - Biocore UMass Medical School
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