Skip Navigation


CIT can broadcast your seminar, conference or meeting live to a world-wide audience over the Internet as a real-time streaming video. The event can be recorded and made available for viewers to watch at their convenience as an on-demand video or a downloadable podcast. CIT can also broadcast NIH-only or HHS-only content.

Transcriptional Mechanisms of Drug Addiction

Loading video...

 
   
Air date: Wednesday, May 06, 2009, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views:
Category: Wednesday Afternoon Lectures
Runtime: 00:54:30
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.
Debug: Show Debug
NLM Title: Transcriptional mechanisms of drug addiction [electronic resource] / Eric Nestler.
Series: NIH director's Wednesday afternoon lecture series
Author: Nestler, Eric J.
National Institutes of Health (U.S.)
Publisher:
Other Title(s): NIH director's Wednesday afternoon lecture series
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: Lectures
Webcasts
Download: To download this event, select one of the available bitrates:
[384k]    How to download a Videocast
NLM Classification: WM 270
NLM ID: 101507191
CIT Live ID: 7045
Permanent link: http://videocast.nih.gov/launch.asp?15089

 

Podcast information
Audio Podcasts   Video Podcasts
  Description Runtime     Description Runtime
Listen to the podcast Enhanced Audio Podcast 54:31   Watch the podcast Enhanced Video Podcast 54:31