Although FN-439 has been extensively characterized and repeatedly been shown to attenuate the effects of MMPs on the ECM and reduce various indices of associative and non-associative learning (including the underlying processes necessary for such learning to occur; Brown et al., 2007; Brown et al., 2009; Meighan et al., 2006; Wiediger et al., 2009; Wright et al., 2007), it is considered a general MMP inhibitor and does not allow for the precise specification of which MMPs are relevant to particular behaviors. Although the MMP family consists of over 25 enzymes, MMP-9 and MMP-3 have been heavily implicated in systems that could contribute to escalated responding and negative reinforcement learning. MMP-9 is required for the synaptic plasticity related to hippocampal-based long-term potentiation and memory (Nagy et al., 2006) and is involved in dendritic spine enlargement through a β1-integrin pathway (Wang et al., 2008). Furthermore, MMP-9 levels are increased following cocaine-primes in a reinstatement paradigm (Brown, Forquer, Harding, Wright, & Sorg, 2008), have been shown to be altered in the hippocampus by chronic cocaine exposure (Mash et al., 2007) and are increased
