Researchers find brain mechanism that leads to cocaine addiction

Researchers have identified a new molecular mechanism that alters the brain’s reward circuits after an individual has consumed cocaine.

Detailed in the journal Proceedings of the National Academy of Science, the discovery could provide a potential drug target for anti-addiction medications.

When administering chronic cocaine to lab mice, the research team from Icahn School of Medicine at Mount Sinai saw increased levels of an enzyme called PARP-1, which led to an increase in its RAR marks at genes in the nucleus accumbens.  These epigenetic changes altered the activity of the nucleus accumbens, ultimately contributing to long-term addiction to cocaine.

According to Kimberly Scobie, lead investigator and postdoctoral fellow, inhibiting PARP-1 could help to mediate the brain’s reward center.

"It is striking that changing the level of PARP-1 alone is sufficient to influence the rewarding effects of cocaine," Scobie said.

The researchers also found that the epigenetic changes induced by PARP-1 changed the expression of sidekick-1, a cell adhesion molecule found on the brain’s synapses.  Overexpression of sidekick-1 both increased the rewarding effects of cocaine and caused changes in synaptic connections of neurons in the brain reward region.