Researchers report that the level of enzyme histone deacetylase 5 (HDAC5) is reduced in chronic cocaine use as well as stressful situations causing the brain to descend into a pathological state.
The team’s previous studies showed that chronic cocaine administration in mice increased acetyl groups in a brain region called the nucleus accumbens (NAc). These areas are known to be involved in response to cocaine and stress. HDAC5 normally represses specific genes by removing acetyl groups from the histone proteins that make up the chromatin surrounding them.
In the current research, the investigators examined the effects of chronic cocaine or stress on HDAC5. They say that the tests showed a reduction in HDAC5, allowing some 172 genes to be activated. They also found that this loss of HDAC5 in the NAc made the mice more sensitive to the reward from continuously using cocaine.
To study HDAC5’s link to stress, the scientists also exposed some mice to other more aggressive mice and measured the resulting depressive behavior. The researchers report finding that such stress also reduced HDAC5 function although through a different mechanism.
The work was done by scientists at the University of Texas Southwestern Medical Center, University of California, Santa Barbara, University of Harvard, Harvard Medical School, McLean Hospital, and Gilead Sciences. The paper will be published in the November 8 issue of Neuron.