Document Detail


Modulation of chromatin modification facilitates extinction of cocaine-induced conditioned place preference.
MedLine Citation:
PMID:  19765687     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Melissa Malvaez; Carles Sanchis-Segura; Darren Vo; K Matthew Lattal; Marcelo A Wood
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biological psychiatry     Volume:  67     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-02-25     Revised Date:  2012-01-06    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36-43     Citation Subset:  IM    
Affiliation:
Department of Neurobiology and Behavior, University of California, Irvine, Center for the Neurobiology of Learning and Memory, Irvine, California 92697-3800, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Butyrates / pharmacology
Chromatin / drug effects,  metabolism*
Cocaine / administration & dosage*
Conditioning, Operant / drug effects*
Dopamine Uptake Inhibitors / administration & dosage*
Extinction, Psychological / drug effects,  physiology*
Gene Expression Regulation, Enzymologic / drug effects
Histone Deacetylase Inhibitors / pharmacology
Histones / metabolism
Male
Mice
Mice, Inbred C57BL
Nucleus Accumbens / drug effects
Reinforcement Schedule
Grant Support
ID/Acronym/Agency:
R01 DA025922-01/DA/NIDA NIH HHS; R01DA025922/DA/NIDA NIH HHS; R01MH077111/MH/NIMH NIH HHS; R01MH081004/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Butyrates; 0/Chromatin; 0/Dopamine Uptake Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Histones; 50-36-2/Cocaine
Comments/Corrections
Comment In:
Epigenomics. 2010 Apr;2(2):183-6   [PMID:  22121869 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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