It has been reported that the levels of MeCP2 are closely related to those of, BDNF (Chang et al., 2006). However, the complex mechanisms by which MeCP2 regulates BDNF levels remain unclear. BDNF in the striatum is known to increase the motivational properties of cocaine (Horger et al., 1999; Schoenbaum et al., 2007). We therefore hypothesized that miR-212-MeCP2 interactions may regulate cocaine intake by influencing levels of BDNF in striatum. We observed that virus-mediated MeCP2 knockdown or miR-212 expression (which decreases MeCP2 levels) in striatum reduced BDNF expression. Moreover, virus-mediated increases in BDNF expression in striatum increased cocaine intake in rats with extended but not restricted access. Conversely, disruption of striatal BDNF signaling using a neutralizing antibody reduced cocaine intake in extended but restricted access rats (Im et al., 2010). These findings suggest that miR-212-MeCP2 interactions may determine expression levels of BDNF in striatum, which in turn regulates the motivational properties of cocaine.
