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. Author manuscript; available in PMC: 2014 Dec 2.
Published in final edited form as: Mol Psychiatry. 2011 May 24;16(12):1159–1168. doi: 10.1038/mp.2011.58

Figure 1.

Figure 1

Relation between miR-212, methyl CpG-binding protein (MeCP2), and brain-derived neurotrophic factor (BDNF) mediates the adaptive response to chronic cocaine exposure. Cocaine increases BDNF concentrations, even after a single dose,78 and BDNF has a strong role in the motivating and rewarding aspects of the drug.86 BDNF signaling at the synapse increases transcription of miR-212 via an extracellular-signal-related kinase (ERK1/2) pathway.37 This miRNA exhibits mutual inhibition with MeCP2, a transcription factor necessary for BDNF expression in response to neural activity.74 The increased expression of miR-212 observed after chronic cocaine treatment72 therefore represents a mechanism of tolerance by inhibiting activity-dependent BDNF transcription in the nucleus accumbens.