Horger et al., 1999; Lu et al., 2004a) can reversibly modulate behavior and synaptic plasticity (Pu et al., 2006) associated with relapse to cocaine-seeking behavior. However, the effects of growth factors may differ among brain regions, since BDNF in the prefrontal cortex can decrease drug seeking (McGinty et al., 2009). Although the precise mechanisms through which BDNF and GDNF modulate drug seeking remain unclear, altered AMPAR signaling is an interesting possibility. For example, LTP induction is facilitated by an AMPAR-mediated increase in BDNF release and signaling at excitatory synapses (Jourdi et al., 2009; Lauterborn et al., 2009), and, conversely, BDNF can enhance LTP induction (Barco et al., 2005; Pu et al., 2006). BDNF signaling through the mammalian target of rapamycin (mTor) can increase dendritic mRNA translation, which, along with LTP, facilitates memory formation (Jourdi et al., 2009; Lauterborn et al., 2009; Slipczuk et al., 2009). Moreover, BDNF signals through ERK to increase AMPAR GluA1 subunit synaptic delivery (Li and Keifer, 2009). Thus, growth factors such as BDNF and GDNF have multiple pathways through which they can enhance AMPAR function, facilitate memory formation, and in this way stabilize memories that drive drug seeking even after prolonged abstinence from drugs.
