Investigators at The Scripps Research Institute in Jupiter, Florida, say that they have found an miRNA that plays a role in cocaine addiction. The same miRNA identified in this study is also expressed in the human dorsal striatum, a brain region that has been linked to drug abuse and habit formation.
Their research revealed that miRNA-212 levels are increased after cocaine consumption in the brains of some rats. At higher levels the rats exhibited a growing dislike for cocaine, ultimately controlling how much they consumed. By contrast, as levels of miRNA-212 decreased, the rats consumed more cocaine and became the rat equivalent of compulsive users.
Details appear in a Nature paper titled “Striatal MicroRNA Controls Cocaine Intake Through Regulation of CREB Signaling.” Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signaling, the authors write.
This action occurs through miR-212-enhanced Raf1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (transducer of regulated CREB, or CRTC).
Findings suggest that striatal miR-212 signaling has a key role in determining vulnerability to cocaine addiction and point to new molecular regulators that control the actions of cocaine in brain reward circuitries.