Researchers have pinpointed the "molecular mechanism" responsible for cocaine addiction; the finding could help them tackle the problem with a drug.
The mechanism "alters the brain's reward circuits and causes addiction," a Mount Sinai Hospital news release reported. The team determined how an "abundant enzyme and synaptic gene" affect the brain's reward center which changes how genes are expressed in the nucleus accumbens.
"This discovery provides new leads for the development of anti-addiction medications," senior author, Eric Nestler, MD, PhD, Nash Family Professor of Neuroscience and Director of the Friedman Brain Institute, at the Icahn School of Medicine at Mount Sinai, said in the news release.
This does not change the DNA itself, but its "mark" either represses or activates genes which encodes synaptic proteins in the DNA. These marks indicate epigenetic changes (which are created by enzymes) that influence the behavior of the nucleus accumbens.
A research team studied cocaine-addicted mice and found "chronic cocaine administration increased levels of an enzyme called PARP-1 or poly(ADP-ribosyl)ation polymerase-1," the news release reported.
When PARP-1 is increased its PAR marks at the "genes in the nucleus accumbens" increase as well which can lead to cocaine addiction. This study is the first linking PARP-1 to cocaine addiction, but it has been investigated as a cancer treatment in the past.
"It is striking that changing the level of PARP-1 alone is sufficient to influence the rewarding effects of cocaine," Kimberly Scobie, PhD, the lead investigator and postdoctoral fellow in Dr. Nestler's laboratory, said.
The researchers used chromatin immunoprecipitation sequencing to determine which genes were affected by epigenetic changes brought on by PARP-1.
The team found sidekick-1 (a cell adhesion molecule concentrated at synapses that directs synaptic connections) was affected by chronic cocaine use.
The team looked at what happened when sidekick-1 was overexpressed, and found it increased the "rewarding effects" associated with cocaine and caused changes in neurons in the brain's reward region.
"The research opens the door to a brand new direction for therapeutics to treat cocaine addiction. Effective drug therapies are urgently needed. National data from the [U.S.] National Institute of Drug Abuse reveal that nearly 1.4 million Americans meet criteria for dependence or abuse of cocaine," the news release reported.