The potential importance of the restriction of these forms of LTD to one MSN subtype is that in contrast to NMDAR-dependent LTD, the eCB LTD observed in the NAc is dramatically impaired 24 hours following only a single dose of either cocaine or 9-THC (Fourgeaud et al., 2004; Mato et al., 2004). Similarly, the eCB- and TRPV1-dependent LTD in indirect pathway NAc MSNs was absent 24 hours after administration of a single dose of cocaine (Grueter et al., 2010). The inhibition of these forms of LTD by cocaine is consistent with the suggestion that the cocaine treatment impairs postsynaptic mGluR signaling, which is required for the generation of eCB’s in NAc MSNs (Fourgeaud et al., 2004). The behavioral function of these forms of LTD and their block by cocaine is unknown. Interestingly, although basal locomotor activity was normal in knockout mice lacking TRPV1, these mice exhibited an enhanced locomotor response to cocaine that was maintained as behavioral sensitization developed with repeated daily administration of cocaine (Grueter et al., 2010). Assuming that the absence of TRPV1 specifically in NAc indirect pathway
