Promising New Drug Target to Help Reduce Cocaine Addiction

Researchers from the Icahn School of Medicine at Mount Sinai have discovered a new molecular mechanism that could alter reward circuits found in the brain of those addicted to cocaine.

Study results show that though the DNA does not change, it leaves a "mark" on certain genes that encode synaptic proteins within the DNA. These marks indicate epigenetic changes that are made by enzymes and help alter the activity of the nucleus accumbens.

By using a mouse model, the research team found that chronic cocaine administration increased the levels of an enzyme called PARP-1. This increase creates changes in the nucleus accumbens that may alter long-term cocaine addiction, according to studies.

"This discovery provides new leads for the development of anti-addiction medications," said the study's 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, via a press release.She believes that the PARP could be used to help identify other proteins regulated by the drug. 

Kimberly Scobie, PhD, the lead investigator and postdoctoral fellow in Dr. Nestler's laboratory, underscored the value of implicating PARP-1 in mediating 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," she said.

The researchers then used chromatin immunopreciptation sequencing to determine which genes were altered through the epigenetic changes of the enzyme.

The study notes the following, via the release: "One target gene whose expression changed after chronic cocaine use was sidekick-1, a cell adhesion molecule concentrated at synapses that directs synaptic connections. Sidekick-1 has not been studied to date in the brain, nor has it been studied in relation to cocaine exposure. Using viral mediated gene transfer to overexpress sidekick-1 in the nucleus accumbens, investigators saw that this overexpression alone not only increased the rewarding effects of cocaine, but it also induced changes in the morphology and synaptic connections of neurons in this brain reward region."

Researchers believe this may help determine new therapeutic treatments for cocaine addiction.

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More information regarding the study can be found via the journal Proceedings of the National Academy of Sciences.