NIH VideoCast - Transcriptional Mechanisms of Drug Addiction

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Transcriptional Mechanisms of Drug Addiction

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Air date:	Wednesday, May 6, 2009, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 219 * This only includes stats from October 2011 and forward.
Category:	WALS - Wednesday Afternoon Lectures
Runtime:	00:54:30
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Addiction can be viewed as a form of drug-induced neural plasticity. Given the stability of the behavioral abnormalities that characterize an addicted state, it makes sense that stable changes in gene expression are involved. Among several transcriptional mechanisms implicated in drug addiction, our laboratory has focused on two main pathways. First, chronic exposure to cocaine or certain other drugs of abuse causes prolonged activation of the transcription factor CREB within several brain regions, and this adaptation mediates aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed ?FosB, in some of the same brain regions exerts the opposite effect and contributes to sensitized responses to drug exposure. Studies are underway to explore the detailed molecular mechanisms by which CREB and FosB regulate target genes and thereby contribute to the complex state of addiction. One way to approach such molecular mechanisms of drug action in vivo is through the study of chromatin remodeling, that is, changes in the acetylation or methylation of histones that bind to certain drug-regulated gene promoters, or changes in methylation of the promoters themselves, as revealed by chromatin immunoprecipitation (ChIP). We are utilizing ChIP to examine chromatin changes at specific candidate genes for CREB and ?FosB, as well as ChIP on chip (immunoprecipitated chromatin analyzed by gene promoter arrays) to gain a global view of target genes for these transcription factors. We are also investigating drug regulation of some of the enzymes that catalyze chromatin remodeling as additional drug targets. These findings establish chromatin remodeling as an important regulatory mechanism underlying drug-induced neural and behavioral plasticity, and promise to reveal fundamentally new insight into how CREB and ?FosB, and several other transcription factors, contribute to addiction by regulating the expression of specific target genes. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide.

NLM Title:	Transcriptional mechanisms of drug addiction / Eric Nestler.
Author:	Nestler, Eric J. National Institutes of Health (U.S.)
Publisher:
Abstract:	(CIT): Addiction can be viewed as a form of drug-induced neural plasticity. Given the stability of the behavioral abnormalities that characterize an addicted state, it makes sense that stable changes in gene expression are involved. Among several transcriptional mechanisms implicated in drug addiction, our laboratory has focused on two main pathways. First, chronic exposure to cocaine or certain other drugs of abuse causes prolonged activation of the transcription factor CREB within several brain regions, and this adaptation mediates aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed [delta]FosB, in some of the same brain regions exerts the opposite effect and contributes to sensitized responses to drug exposure. Studies are underway to explore the detailed molecular mechanisms by which CREB and FosB regulate target genes and thereby contribute to the complex state of addiction. One way to approach such molecular mechanisms of drug action in vivo is through the study of chromatin remodeling, that is, changes in the acetylation or methylation of histones that bind to certain drug-regulated gene promoters, or changes in methylation of the promoters themselves, as revealed by chromatin immunoprecipitation (ChIP). We are utilizing ChIP to examine chromatin changes at specific candidate genes for CREB and [delta]FosB, as well as ChIP on chip (immunoprecipitated chromatin analyzed by gene promoter arrays) to gain a global view of target genes for these transcription factors. We are also investigating drug regulation of some of the enzymes that catalyze chromatin remodeling as additional drug targets. These findings establish chromatin remodeling as an important regulatory mechanism underlying drug-induced neural and behavioral plasticity, and promise to reveal fundamentally new insight into how CREB and [delta]FosB, and several other transcription factors, contribute to addiction by regulating the expression of specific target genes.
Subjects:	Behavior, Addictive--physiopathology Brain--drug effects Substance-Related Disorders--physiopathology Transcription Factors--physiology
Publication Types:	Lecture Webcast
NLM Classification:	WM 270
NLM ID:	101507191
CIT Live ID:	7045
Permanent link:	https://videocast.nih.gov/watch=7045

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