"The new findings are a significant advance from this previous study," Kenny said, "because they clearly demonstrate why microRNA-212 is not always fully protective because MeCP2 regulates by how much miR-212 levels will increase in response to cocaine. This suggests that our initial findings may be central to explaining the complex process of addiction, and understanding how miR-212 signaling is regulated will be important. This study adds another level of detail to the blueprint."
A major goal of drug abuse research is to understand why certain individuals make the switch from casual to compulsive drug use and develop into addicts. Periods of easy access to the drug, along with repeated overconsumption, can quickly trigger the emergence of addiction-like abnormalities in animal models.
In the new study, the scientists first looked at the expression of MeCP2 in the brain after exposure to cocaine. They found that expression was increased in those animals given extended access to the drug.
"At that point," Kenny said, "we wanted to know if this increase was behaviorally significant did it influence the motivation to take the drug?"
Using a virus to disrupt expression of MeCP2, the scientists found that rats consumed less and less cocaine. Intriguingly, levels of miR-212 were also far higher in those animals. Because increases in miR-212 suppress attraction to cocaine, the disruption of MeCP2, in essence, put miR-212 in charge and reduced vulnerability to the drug.
"We concluded that MeCP2 may play an important role in addiction by regulating the magnitude by which miR-212 expression is increased in response to cocaine," said Kenny. "In other words, MeCP2 seems to control just how much you can protect yourself against the addictive properties of cocaine."
Intriguingly, that was not the end of the story
|Contact: Mika Ono|
Scripps Research Institute