Epigenetic mechanisms in drug addiction

Below is an excerpt on “epigenetic mechanisms in drug addiction” from Bredy, Sun and Kobor’s (2010) review paper on the epigenome and psychological disorders:

EPIGENETIC MECHANISMS INDRUG ADDICTION

Immunostain used to detect acetylated H3K9 in embryonic lung

In recent years, Nestler and coworkers have led the field indescribing how the epigenome contributes to neural andbehavioral adaptation associated with drugs of abuse(Renthal & Nestler, 2008). In their groundbreaking study,Kumar et al. (2005) demonstrate how exposure tobehaviorally relevant doses of cocaine lead to histonemodifications and subsequent expression of several genesknown to be critical for development of drug-seekingbehavior. Acute cocaine exposure induces a time-dependentincrease in H4 acetylation and phospho (Ser10)-acetylated H3K14 around the promoter of the immediateearly gene (IEG) c-Fos with a peak at 30–90 min andreturn to baseline 180 min postcocaine administration.After chronic cocaine exposure, while c-Fos remainsunaffected, there is a significant increase in H3K9 andK14 acetylation around the promoter for the IEG FosB.This effect occurs after both passive cocaine administrationand under conditions of chronic self-administration.Remarkably, histone modifications around both thec-Fos and FosB promoters map on to the time-dependentnature of IEG expression in response to acute and chroniccocaine exposure, which therefore suggests that distinctpatterns of chromatin remodeling are associated withspecific genes that exhibit either acute or long-lastingexpression profiles. Interestingly, FosB codes for thetranscription factor DFosB, which is implicated in thetransition from acute recreational drug use to chronicaddiction (McClung & Nestler, 2003). DFosB bindsdirectly to the promoter of the c-Fos gene after acuteexposure to amphetamine and, in contrast to its permissiveeffect on Cdk5 expression, leads to repression of c-Fosactivity (Renthal et al., 2008). Binding, desensitization,and repression of c-Fos gene expression are mediatedepigenetically by the recruitment of HDAC1 and HTM(KMT1A), and by increased H3K9me2 around the c-Fospromoter. Together, these findings suggest that epigeneticmechanisms participate in feedback loops involving IEGactivity, both histone acetylation and methylation, andexpression of specific genes in response to acute andchronic exposure to drugs of abuse.

To read more see source below:

Bredy TW, Sun YE, Kobor MS. How the epigenome contributes to the development of psychiatric disorders.  (2010) PMID 20127889

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About sociogenomics

I study behaviour and evolution. This space is about sharing with others notable (and sometimes unexpected) findings that relate to my own scientific interests and research.
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