Histone Deacetylase Inhibitors Eliminate Cocaine Sensitization

In the nucleus, DNA wraps around histone proteins, which pack the DNA and makes it less accessible for transcription. Many transcriptional activators promote histone acetylation, which opens the chromatin structure and helps recruit transcription machinery to the newly accessible genes. Conversely, some gene repressors promote deacetylation of histones. Because drug dependence is mediated partly by changes in gene expression, inhibitors of histone acetylation and deacetylation might prevent the development of drug dependence. Romieuet al. support this hypothesis by showing that administering histone deacetylase inhibitors shortly before giving rats access to cocaine reduced cocaine self-administration and decreased the number of times a rat poked its nose in a hole to receive a dose of cocaine. When rats receive cocaine daily, their response to a dose increases over time. This increased responsiveness, called sensitization, is thought to promote dependence. Cocaine sensitization is prevented by histone deacetylase inhibitors, suggesting inhibitors may effectively reduce dependence.

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