(provided by candidate): A small number of drugs and chemical agents can come to control human behavior by producing a state called addiction. The evidence accumulated over the last decade demonstrates that drugs of abuse can co-opt synaptic plasticity mechanisms in brain circuits involved in reinforcement and reward processing. Indeed, an influential hypothesis is that addiction represents a pathological, yet powerful, form of learning and memory. MicroRNAs (miRNAs) are a relatively new class of small noncoding RNAs that play an important role in post-transcriptional gene regulation during development and disease. miRNAs are abundant in the vertebrate nervous system where they appear to function during neuronal fate determination and early differentiation. It is now becoming increasingly clear that miRNAs are also involved in later stages of neuronal development, namely, the formation and plasticity of synapses. The underlying hypothesis of this grant proposal is that dysregulated miRNA expression plays an important role in driving compulsive cocaine-seeking behaviors. The primary goals of the proposed experiments are a) to characterize brain expression patterns of miRNAs in an animal model of compulsive cocaine seeking, b) to characterize miRNAs whose expression is altered by compulsive cocaine intake, c) to assess the functional relevance of miRNAs whose expression is altered by compulsive cocaine seeking by directly modifying their expression levels in vivo. The proposed studies promise to yield significant new insights into the role of miRNAs in regulating compulsive cocaine intake, and may have important clinical utility for the development of novel therapeutics for the treatment of cocaine addiction.
|Schaefer, Anne; Im, Heh-In; Veno, Morten T et al. (2010) Argonaute 2 in dopamine 2 receptor-expressing neurons regulates cocaine addiction. J Exp Med 207:1843-51|