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The Inhibition of Histone Deacetylases Reduces the Reinstatement of Cocaine-Seeking Behavior in Rats

Authors
Journal
Current Neuropharmacology
1570-159X
Publisher
Bentham Science
Publication Date
Volume
9
Issue
1
Identifiers
DOI: 10.2174/157015911795017317
Keywords
  • Article
Disciplines
  • Biology
  • Medicine
  • Pharmacology

Abstract

Drug addiction is a chronic brain disease characterized by a persistent risk of relapse, even after a long period of abstinence. A current hypothesis states that relapse results from lasting neuroadaptations that are induced in response to repeated drug administration. The adaptations require gene expression, some of which being under the control of stable epigenetic regulations. We have previously demonstrated that pretreatment with histone deacetylase (HDAC) inhibitors reduces the cocaine reinforcing properties as well as the motivation of rats for cocaine. We show here that the same HDAC inhibitors, trichostatin A and phenylbutyrate, significantly reduced the cocaine-seeking behavior induced by the combination of a cocaine injection together with the exposure to a light cue previously associated with cocaine taking. Reinstatement of drug-seeking behavior was carried out after a 3-week withdrawal period, which came after ten daily sessions of cocaine intravenous self-administration. Our results suggest that pharmacological treatment aimed at modulating epigenetic regulation, and particularly treatment that would inhibit HDAC activity, could reduce the risk of relapse, a major drawback in the treatment of drug addiction.

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