Featured Research

from universities, journals, and other organizations

Enzyme Regulates Brain Pathology Induced By Cocaine, Stress

Date:
November 9, 2007
Source:
Cell Press
Summary:
Researchers have uncovered a key genetic switch that chronic cocaine or stress influences to cause the brain to descend into a pathological state. In studies with mice they showed how chronic cocaine changes gene activity to enhance the addictive reward from the drug. And they showed similarly how chronic stress induces the same kinds of changes that hypersensitizes the brain, causing depression-like symptoms.

Researchers have uncovered a key genetic switch that chronic cocaine or stress influences to cause the brain to descend into a pathological state. In studies with mice they showed how chronic cocaine changes gene activity to enhance the addictive reward from the drug. And they showed similarly how chronic stress induces the same kinds of changes that hypersensitizes the brain, causing depression-like symptoms.

The researchers said their basic finding in the animals could lead to better treatments for addiction, depression and other psychiatric disorders.

In their experiments, the researchers explored how chronic cocaine or stress exerts "epigenetic" control of genes in the brain. Such control involves repressing or activating genes by altering the structure of the chromatin that enwraps genes. Specifically, the researchers explored whether chronic cocaine or stress affect an enzyme called histone deacetylase 5 (HDAC5). Normally, HDAC5 represses specific genes by removing molecules called acetyl groups from the histone proteins that make up the chromatin surrounding them. The researchers' previous studies had shown that chronic cocaine administration in mice caused an increase in acetyl groups in a brain region called the nucleus accumbens (NAc), known to be involved in response to cocaine or stress.

The researchers' studies showed that giving mice chronic cocaine led to a reduction in HDAC5, allowing some 172 genes to be activated. What's more, they found that this loss of HDAC5 in the NAc made the mice more sensitive to the reward of chronic cocaine. They determined the animals' reward-sensitivity to cocaine by measuring the mice's preference for an area of a box that they were taught to associate with receiving cocaine.

The researchers also studied whether the animals' adaptation to chronic stress involved HDAC5 levels. In these experiments, they exposed mice to aggressive mice and measured the resulting depressive behavior. The researchers found that such stress also reduced HDAC5 function, although through a different mechanism than for chronic cocaine.

"These data demonstrate a crucial role for HDAC5 in regulating behavioral adaptations to chronic stress as well as chronic cocaine and suggest that HDAC5 contributes to a molecular switch between acute stress responses and more long-lasting depression-like maladaptations," wrote the researchers.

"The functions of HDAC5 described here provide new insight into the pathogenesis of drug addiction, depression, and other stress-related syndromes," they wrote. "This fundamentally new insight into the molecular underpinnings of chronic maladaptation in brain could lead to the development of improved treatments for addiction, depression, and other chronic psychiatric disorders."

Eric Nestler and colleagues published their findings in the November 8, 2007, issue of the journal Neuron, published by Cell Press.

The researchers include Eric J. Nestler,William Renthal, Ian Maze, Vaishnav Krishnan, Herbert E. Covington, III, Arvind Kumar, Rhonda Bassel-Duby, Eric N. Olson, Scott J. Russo, Ami Graham, Nadia Tsankova, Guanghua Xiao, of the The University of Texas Southwestern Medical Center, Dallas, TX. USA; Tod E. Kippin, and Kerry A. Kerstetter, of the Department of Psychology, University of California, Santa Barbara, Santa Barbara, CA, USA; Rachael L. Neve, of Harvard Medical School and McLean Hospital, in Belmont, MA, USA; Stephen J. Haggarty, of the Department of Chemistry and Chemical Biology, Harvard University, in Cambridge, MA, USA; and Timothy A. McKinsey, of Myogen, Inc./Gilead Colorado, Inc.,Westminster, CO, USA.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Enzyme Regulates Brain Pathology Induced By Cocaine, Stress." ScienceDaily. ScienceDaily, 9 November 2007. <www.sciencedaily.com/releases/2007/11/071107160227.htm>.
Cell Press. (2007, November 9). Enzyme Regulates Brain Pathology Induced By Cocaine, Stress. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2007/11/071107160227.htm
Cell Press. "Enzyme Regulates Brain Pathology Induced By Cocaine, Stress." ScienceDaily. www.sciencedaily.com/releases/2007/11/071107160227.htm (accessed July 31, 2014).

Share This




More Mind & Brain News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dieting At A Young Age Might Lead To Harmful Health Habits

Dieting At A Young Age Might Lead To Harmful Health Habits

Newsy (July 30, 2014) Researchers say women who diet at a young age are at greater risk of developing harmful health habits, including eating disorders and alcohol abuse. Video provided by Newsy
Powered by NewsLook.com
It's Not Just Facebook: OKCupid Experiments With Users Too

It's Not Just Facebook: OKCupid Experiments With Users Too

Newsy (July 29, 2014) If you've been looking for love online, there's a chance somebody has been looking at how you're looking. Video provided by Newsy
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins