Finally, we recently disrupted BDNF signaling in the two MSNs by deleting its TrkB receptor selectively from each MSN subtype. We observed opposite effects on cocaine-elicited behaviors: cocaine-induced locomotor activity and the induction of cocaine CPP were enhanced after TrkB deletion from D1+ MSNs, but attenuated after deletion from D2+ MSNs (Lobo et al., 2010). Interestingly, the deletion of TrkB from D2+ MSNs mimics the effects of total deletion of TrkB from the NAc as well as disruption of BDNF signaling from the VTA (Horger et al., 1999; Graham et al., 2007, 2009; Bahi et al., 2008; Crooks et al., 2010). These findings thus show for the first time a predominant role of a signaling cascade in D2+ MSNs in mediating the effects of a drug of abuse. The predominant role of D2+ MSNs in mediating BDNF’s effects on cocaine-elicited behaviors is not surprising considering both TrkB mRNA and protein are enriched in D2+ MSNs (Lobo et al., 2010; Baydyuk et al., 2011). The behavioral changes observed in these mice were accompanied by enhanced neuronal activity in the D2+ MSNs
