Research Review

Researchers Uncover Early Step in the Brain Events Leading to Addiction

A regulatory protein best known for its role in a rare genetic brain disorder also may play a critical role in cocaine addiction, according to a recent study in rats, funded by the National Institute on Drug Abuse. The study was published in Nature Neuroscience.

Researchers at the Scripps Research Institute in Jupiter, FL, found that cocaine consumption increased levels of a regulatory protein called MeCP2 that shuttles back to the nucleus to influence gene expression in rat brains. As levels of MeCP2 increased in the brain, so did the animals' motivation to self-administer cocaine. This suggests that MeCP2 plays a crucial role in regulating cocaine intake in rats and perhaps in determining vulnerability to addiction.

This is the second time this year that a critical factor related to cocaine self-administration in rodents has been identified. In a study published in Nature, Scripps researchers identified regulatory molecule miRNA-212 as playing a key role in cocaine intake. However, MeCP2 increased motivation for cocaine, whereas miRNA-212 had the opposite effect, suggesting that the latter plays a protective role against drug seeking.

In the current study, researchers discovered that the brain's balance between MeCP2 and miRNA-212 ultimately regulates cocaine intake. When the balance shifts toward MeCP2, cocaine intake increases. When the balance shifts toward miRNA-212, cocaine intake decreases. What determines the balance is not yet understood, however, and will be the focus of future research.

"This study represents another piece in the puzzle of determining vulnerability to cocaine addiction," says Paul J. Kenny, PhD, senior study author and an associate professor at Scripps. "If we can continue putting the pieces together, we may be able to determine whether there are viable treatments for this condition."

— Source: The National Institute on Drug Abuse