Extended cocaine-taking triggers a number of structural and functional changes in the brain that may lead to compulsive drug seeking, but the mechanisms that regulate the process are unclear. Experiments in rats now reveal a fundamental role for microRNAs in the striatum in governing the development of compulsive cocaine-seeking behaviour. The microRNA miR-212 decreases cocaine seeking, but only in rats that have taken the drug for an extended amount of time, and not in non-drug-dependent rats. miR-212 appears to act by amplifying the activity of the transcription factor CREB, a known regulator of the rewarding effects of cocaine. This work raises the possibility that agents that modulate the action of noncoding RNAs might be effective in reversing drug addiction. [Article p. 197; News & Views p. 194]
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