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Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats.

Pascal Romieu1, Lionel Host, Serge Gobaille

  • 1Inserm, U575, Centre de Neurochimie, 67084 Strasbourg, France, Institut Fédératif de Recherche 37 Neurosciences, 67085 Strasbourg, France. romieu@neurochem.u-strasbg.fr

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|September 19, 2008
PubMed
Summary
This summary is machine-generated.

Histone deacetylase (HDAC) inhibitors reduced cocaine self-administration and motivation in rats, suggesting epigenetic regulation influences drug dependence. This approach did not affect natural rewards, highlighting its specific impact on addiction-related behaviors.

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Area of Science:

  • Neuroscience
  • Epigenetics
  • Pharmacology

Background:

  • Gene expression regulation is crucial for long-term adaptations to drugs of abuse.
  • Chromatin remodeling, involving histone modifications, regulates gene transcription in neurons.

Purpose of the Study:

  • To investigate the role of epigenetic regulation, specifically histone deacetylase (HDAC) inhibition, in the reinforcing properties of drugs.
  • To determine if HDAC inhibition affects motivated behavior for cocaine versus natural rewards.

Main Methods:

  • Rats underwent cocaine operant self-administration under fixed and progressive ratio schedules.
  • HDAC inhibitors (trichostatin A, phenylbutyrate, depudecin) were administered.
  • HDAC activity was measured in the frontal cortex.
  • Locomotion and sucrose preference tests were used for control experiments.
  • Cocaine-induced behavioral sensitization was assessed.

Main Results:

  • HDAC inhibitors dose-dependently reduced cocaine self-administration and attenuated motivation for cocaine.
  • HDAC inhibition did not affect self-administration of sucrose, a natural reinforcer.
  • HDAC activity in the frontal cortex was inhibited by cocaine but not sucrose.
  • HDAC inhibition did not cause general motivational dysfunction or anhedonia.
  • HDAC inhibition blocked cocaine-induced behavioral sensitization.

Conclusions:

  • Epigenetic regulation via HDAC inhibition can influence motivated behavior in the adult brain.
  • HDAC inhibition shows potential in counteracting neural sensitization associated with drug dependence.
  • Targeting epigenetic mechanisms may offer novel therapeutic strategies for addiction.