Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find alterations in brain’s circuitry caused by cocaine

24.10.2005


Cocaine causes specific alterations in the brain’s circuitry at a genetic level, including short-term changes that result in a high from the cocaine, as well as long-term changes seen in addiction, researchers from UT Southwestern Medical Center have found.



Such findings suggest possible new directions for treatments for addiction to the drug, they said.

In a study available online and in the Oct. 20 issue of Neuron, UT Southwestern researchers used rodents to pinpoint an important molecular mechanism that switches genes "on" in the part of the brain involved in drug-induced rewards. They also determined that cocaine, through a process called "chromatin remodeling," alters the normal biochemical processes that allow these specific genes to be turned on and off.


"Our study provides a fundamentally new level of analysis by which we can better understand the actions of cocaine in brain-reward regions at the molecular level," said senior author Dr. Eric Nestler, chairman of UT Southwestern’s Department of Psychiatry. "It also points to new potential treatments for addiction."

In order for genes to be activated, or "expressed," proteins called transcription factors have to be able to access the gene and copy its instructions for making other proteins. Typically, a group of proteins called histones tightly binds genes, keeping them from being accessed by transcription factors. Normally, histones undergo chemical changes to convert them from tightly binding a gene to a state where they
are less bound and no longer inhibit gene expression.

However, through chromatin remodeling - or modifying the genetic material located in the cell’s nucleus - cocaine chemically alters histones, causing them to loosen their "grip" on certain genes and allowing transcription factors to turn the genes on, the researchers found.

"Our study was the first to examine histone changes on particular genes in brain-reward regions known to be important for cocaine addiction," said Dr. Nestler, who holds the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research. "We have shown that several genes known to be activated by acute or chronic cocaine use indeed show changes in histone chemical modifications that lead to the genes’ activation."

Another discovery was that chronic cocaine use causes chemical changes to a different type of histone than acute cocaine use does, which may help explain why the behavioral effects of acute versus chronic cocaine use in people are so different, Dr. Nestler said.

Researchers learned, through administering single doses and repeated doses of cocaine to groups of rats and mice, that some of the changes in histones caused by the drug are quite stable, lasting for more than a week after the last cocaine dosage. From that, they concluded that chronic cocaine use may cause long-lasting changes in the brain’s circuitry, whereas short-term use affects genes differently.

"One of the cardinal features of addiction is how long-lived it is," Dr. Nestler said. "A key question in the field has been: By what mechanisms do drugs of abuse cause changes in the brain that last this long?"

Researchers have hypothesized that one such mechanism could be regulation of gene expression and have shown that several transcription factors are regulated by drugs of abuse. This study, however, ventures a step further, providing evidence that histone changes on particular genes are a paramount part of the addiction process.

The researchers also showed that they could reduce or enhance cocaine’s behavioral effects in animals by directly and artificially influencing histone changes with different types of chemicals. One chemical modified histones in a way that increased the animals’ reward response from cocaine, while rats given a different type of chemical, which modified histones in another way, showed decreased rewarding effects.

"We are seeing for the first time how certain genes in the reward center of the brain are regulated by chromatin modifications," said Dr. Arvind Kumar, the study’s lead author and an instructor of psychiatry. "Now that we understand the mechanism of how these stable, cocaine-induced changes in the brain are regulated, this may help us find targets that can be manipulated for future treatment of cocaine addiction."

Other researchers from UT Southwestern’s Department of Psychiatry contributing to the study included Dr. Kwang-Ho Choi, instructor; William Renthal and Nadia Tsankova, Medical Scientist Training Program students; David Theobald and Kimberly Whisler, research associates; Teresa Sasaki and Hoang-Trang Truong, research assistants; Dr. Scott Russo, postdoctoral research fellow; Quincey LaPlant, graduate student fellow/medical student; and Dr. David Self, associate professor. A researcher from Harvard Medical School also contributed.

The study was supported by grants from the National Institute on Drug Abuse and the National Institute of Mental Health.

Donna Steph Hansard | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Studies and Analyses:

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

nachricht Urbanization to convert 300,000 km2 of prime croplands
27.12.2016 | Mercator Research Institute on Global Commons and Climate Change (MCC) gGmbH

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>