Background and Aim: Alcohol alters several neurotransmitter
systems within the brain and accumulated
evidences indicate the endogenous opioid system as an
important target of its action. We studied, in vitro and in
vivo the molecular alterations occurring in the prodynorphin
gene following different exposures to alcohol.
Methods: Human neuroblastoma SH-SY5Y cells were
exposed to low, clearly not intoxicating, and high etha-
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European Opioid Conference 2011, Krak\uf3w, Poland
nol concentrations at different time points. Sprague
Dawley rats received alcohol intragastrically trying to
mimic human drinking that establishes tolerance and dependence
conditions. Real-time RT-PCR was used to assess
the abundance of mRNAs of interest. DNA methylation
was analyzed by Methylation Specific-Real Time
PCR and bisulfite-Pyrosequencing. Specific histone
modifications at gene promoters were evaluated by
Chromatin ImmunoPrecipitation.
Results: In the cellular model we demonstrated
a temporal relationship between selective chromatin
modifications induced by ethanol or acetaldehyde,
and changes in prodynorphin gene expression were
demonstrated. In the amygdala complex of alcoholtreated
rats differential changes in prodynorphin gene
expression changes were observed depending on the
time of exposure; consistently, we propose potential
epigenetic mechanisms responsible for these alterations,
at least upong short ethanol exposure.
Conclusion: Our findings indicate a linkage between
gene expression alterations and epigenetic modulation
in prodynorphin promoter, thus adding novel information
on how the opioid system can be affected by alcohol
in several ways. Studies are ongoing to evaluate
the chromatin remodelling in the neuroplasticity occurring
in the progression of alcohol abuse. It will be
also of value to study the ability of epigenetic modulators
in reverting dynorphin genetic/epigenetic alterations
and alcohol abuse-related behaviours. Moreover,
opioid drugs already available in alcoholism treatment
could also have possible epigenetic modulating
properties