Cocaine Remakes the Brain

Cocaine alters gene expression in brain cells, and the results depend on whether the drug is used on a short-term or chronic basis, according to researchers at the University of Texas Southwestern Medical Center and Harvard Medical School (Neuron 2005, 48, 303). UT Southwestern’s Eric J. Nestler and Arvind Kumar and colleagues found that cocaine chemically alters histones—the spools around which DNA is wound—through acetylation and phosphoacetylation. These modifications loosen up the DNA and expose genes that can then be transcribed into proteins. Brief cocaine usage increases production of cFos and FosB proteins; long-term usage boosts production of FosB. FosB accumulates in the brain and causes cocaine cravings in addicts. The researchers found that FosB enhances production of Cdk5, which is implicated in rewiring the brain’s reward circuitry. Long-term cocaine use also raises levels of brain-derived neurotrophic factor, which appears to be associated with cocaine-induced changes in behavior and in brain cell structure and function.