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.
Eric Nestler and colleagues published their findings in the November 8, 2007, issue of the journal Neuron, published by Cell Press.
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.”
Cathleen Genova | EurekAlert!
Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)
CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
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...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
19.01.2017 | Earth Sciences
19.01.2017 | Life Sciences
19.01.2017 | Physics and Astronomy