How does cocaine grow on people so much so that it becomes difficult to quit?
Researchers from the Icahn School of Medicine at Mount Sinai have identified a new molecular mechanism by which cocaine alters the brain's reward circuits and causes addiction.
The research opens the door to a brand new direction for therapeutics to treat cocaine addiction.
Published in the journal Proceedings of the National Academy of Sciences, the research reveals how an abundant enzyme and synaptic gene affect a key reward circuit in the brain, changing the ways genes are expressed in the nucleus accumbens.
The DNA itself does not change, but its "mark" activates or represses certain genes encoding synaptic proteins within the DNA.
The marks indicate epigenetic changes - changes made by enzymes - that alter the activity of the nucleus accumbens.
"This discovery provides new leads for the development of anti-addiction medications," said study author Eric J. Nestler.
In a mouse model, the research team found that chronic cocaine administration increased levels of an enzyme called PARP-1. This increase in PARP-1 leads to an increase in its PAR marks at genes in the nucleus accumbens, contributing to long-term cocaine addiction.
PARP inhibitors may also prove valuable in changing cocaine's addictive power.
Lead investigator Kimberly Scobie underscored the value of implicating PARP-1 in mediating the brain's reward centre.
"It is striking that changing the level of PARP-1 alone is sufficient to influence the rewarding effects of cocaine," she said.
