Scripps Research scientists uncover previously unknown natural mechanism that controls c... (used a virus to drive a large over-expre...)

Scripps Research scientists uncover previously unknown natural mechanism that controls cocaine use

Date:7/7/2010

used a virus to drive a large over-expression of the microRNA, there was no effect on the behavior of the limited-access animals," Kenny said. "In the extended-access animals, however, their behavior changed abruptly they took less and less cocaine. In fact, their intake became so low that it appeared they actively disliked the drug. Conversely, when we blocked the actions of the microRNA, the extended access animals began to consume the drug in a compulsive-like manner. MicroRNA-212 is therefore a protective factor helping to prevent the loss of control over drug-taking behavior. Individual differences in microRNA-212 signaling are therefore likely to play a key role in determining vulnerability to cocaine addiction."

In the study, the scientists took their investigation a step further to examine the molecular signaling mechanisms producing this effect. The scientists found that extended consumption of cocaine was associated with an overstimulation of various neurotransmitters in the brain, which increased the production of cAMP (a messenger associated with many biological processes), which in turn activated CREB signaling. (CREB is a transcription factor, a protein that turns on a gene by binding to it, known to regulate how much you like or dislike cocaine.) These changes led to the increase in expression of microRNA-212.

Surprisingly, the scientists found that the increases in microRNA-212 induced by CREB in turn dramatically amplified the actions of cocaine on CREB signaling, establishing a CREB-microRNA-212 "loop." In effect, the microRNA stimulated the pathway in the brain that increases aversive reactions to cocaine, thereby decreasing the motivation to consume the drug.

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Contact: Mika Ono
mikaonomail@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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