One of the major challenges of cocaine addiction is
the high rate of relapse after periods of withdrawal
and abstinence. But new research reveals that
changes in our DNA during drug withdrawal may offer
promising ways of developing more effective
treatments for addiction.
Withdrawal from drug use results in reprogramming of
the genes in the brain that lead to addictive
personality, say researchers from McGill University
and Bar Ilan University in a new study published in
the Journal of Neuroscience.
“We inherit our genes from our parents and these
genes remain fixed throughout our life and are
passed on to our children; we can do very little to
change adverse genetics changes that we inherit,”
says Moshe Szyf, a professor in the Faculty of
Medicine at McGill, “In contrast, epigenetic marks
such as DNA methylation act as switches and dimmers
of genes- they can be switched on, off, or dimmed -
by epigenetic drugs inhibiting DNA methylation and
removing methyl marks from these genes.”
The researchers wanted to see if they could stop
addictive behavior by influencing the epigenetic
markers that were triggered by withdrawal using
epigenetic drugs such as the DNA methylation
inhibitor, RG108.
The team used a rat model of incubation of cocaine
craving, in which rats were trained to
self-administer cocaine which was cued by a specific
light or sound. This drug craving or “addictive”
behavior was tested after either 1 day or 30 days of
withdrawal from cocaine. Following the long
withdrawal, the rats developed an intense drug
seeking behavior when exposed to the cue. It was
after a lengthy period without the drugs that the
epigenetic changes were most evident.
“We discovered that injecting the drug RG108 just
before the animals were exposed to the light cue
after the long withdrawal not only stopped the
addictive behavior of the animals, it also lasted
for a longer period. This suggests that a single
treatment with RG108 could reverse or perhaps cure
drug addiction.” adds Szyf.
“Surprisingly, we discovered that the biggest
changes in DNA methylation occurred not during the
exposure to the drug but during withdrawal,” says
co-author Gal Yadid, of Bar Ilan University, “During
this period of withdrawal, hundreds of genes changed
their state of DNA methylation including genes that
were known before to be involved in addiction”.
“The mainstay of current approaches to treating
addiction might actually aggravate it,” says Yadid.
“Our research suggests that because the changes in
addiction involve numerous genes, our current
approaches will continue to fail if we target one or
few targets in the brain, but more research is
needed to confirm if these new avenues hold
promise.”
For more information
"Role of DNA Methylation in the Nucleus Accumbens in
Incubation of Cocaine Craving" Renaud Massart, Royi
Barnea, Yahav Dikshtein, Matthew Suderman, Oren Meir,
Michael Hallett, Pamela Kennedy and Eric J. Nestler.
Moshe Szyf, Gal Yadid, Journal of Neuroscience.
http://www.jneurosci.org/content/35/21/8042.full.pdf+html
McGill University
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