Modulation of Chromatin Modification Facilitates Extinction of Cocaine-Induced Conditioned Place Preference

Melissa Malvaez, Carles Sanchis-Segura, Darren Vo, Kennon (Matt) Lattal, Marcelo A. Wood

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Background: Recent evidence suggests that epigenetic mechanisms have an important role in the development of addictive behavior. However, little is known about the role of epigenetic mechanisms in the extinction of drug-induced behavioral changes. In this study, we examined the ability of histone deacetylase (HDAC) inhibitors to facilitate extinction and attenuate reinstatement of cocaine-induced conditioned place preference (CPP). Methods: C57BL/6 mice were subject to cocaine-induced CPP using 20 mg/kg dose. To facilitate extinction, mice were administered an HDAC inhibitor following nonreinforced exposure to the conditioned context. To measure persistence, mice were subject to a reinstatement test using 10 mg/kg dose of cocaine. Results: We demonstrate that HDAC inhibition during extinction consolidation can facilitate extinction of cocaine-induced CPP. Animals treated with an HDAC inhibitor extinguished cocaine-induced CPP both more quickly and to a greater extent than did vehicle-treated animals. We also show that the extinction of cocaine seeking via HDAC inhibition modulates extinction learning such that reinstatement behavior is significantly attenuated. Acetylation of histone H3 in the nucleus accumbens following extinction was increased by HDAC inhibition. Conclusions: This study provides the first evidence that modulation of chromatin modification can facilitate extinction and prevent reinstatement of drug-induced behavioral changes. These findings provide a potential novel approach to the development of treatments that facilitate extinction of drug-seeking behavior.

Original languageEnglish (US)
Pages (from-to)36-43
Number of pages8
JournalBiological Psychiatry
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Cocaine
Chromatin
Histone Deacetylase Inhibitors
Histone Deacetylases
Epigenomics
Drug-Seeking Behavior
Psychological Extinction
Addictive Behavior
Aptitude
Nucleus Accumbens
Acetylation
Inbred C57BL Mouse
Pharmaceutical Preparations
Histones
Learning

Keywords

  • Chromatin
  • cocaine
  • conditioned place preference
  • extinction
  • histone deacetylase
  • reinstatement

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Modulation of Chromatin Modification Facilitates Extinction of Cocaine-Induced Conditioned Place Preference. / Malvaez, Melissa; Sanchis-Segura, Carles; Vo, Darren; Lattal, Kennon (Matt); Wood, Marcelo A.

In: Biological Psychiatry, Vol. 67, No. 1, 01.01.2010, p. 36-43.

Research output: Contribution to journalArticle

Malvaez, Melissa ; Sanchis-Segura, Carles ; Vo, Darren ; Lattal, Kennon (Matt) ; Wood, Marcelo A. / Modulation of Chromatin Modification Facilitates Extinction of Cocaine-Induced Conditioned Place Preference. In: Biological Psychiatry. 2010 ; Vol. 67, No. 1. pp. 36-43.
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