disrupting such genes in D2+ MSNs often causes an opposite response (Fienberg et al., 1998; Kelz et al., 1999; Deroche-Gamonet et al., 2003; Zachariou et al., 2006; Ambroggi et al., 2009; Bateup et al., 2010). Nonetheless, we cannot rule out an important contribution of the D2+ MSNs in adaptations to drugs of abuse, because cocaine exposure alters gene expression in both MSN subtypes (Heiman et al., 2008) and D2-receptor agonists and antagonists exert potent effects in behavioral assays (Self, 2010). Indeed, recent findings show that molecular signaling adaptations in D2+ MSNs potently modify an animal’s behavioral response to drugs of abuse (Lobo et al., 2010). The latter findings showed that loss of TrkB (the receptor for BDNF) in D2+ MSNs results in similar behavioral responses to cocaine as total TrkB knockout from the NAc, showing for the first time a selective dominant role for a molecular pathway in D2+ MSNs in mediating the effects of drugs of abuse.
