There are several molecular changes that emerge during abstinence from psychostimulant exposure that are not apparent in drug-naive animals or after recent drug exposure (Kalivas and O’Brien, 2008; Lu et al., 2004b). Some of these enduring molecular events, such as the increased AMPAR function, are hypothesized to drive the motivation to seek drug during relapse (Grimm et al., 2001; Kalivas, 2009; Nestler, 2001). In particular, mRNA for the brain-derived neurotrophic factor (BDNF) increases across abstinence in brain structures such as the NAcb and VTA (Filip et al., 2006; Grimm et al., 2003) and both BDNF and the related glial cell line-derived neurotrophic factor (GDNF) could support the increased motivation for drugs that develops across abstinence (Grimm et al., 2003; Lu et al., 2009). For example, GDNF (Li and Keifer, 2009) and BDNF (Berglind et al., 2007; Graham et al., 2007; 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
