To test the hypothesis that MMPs are required for dependence-induced escalation of self-administration during acute withdrawal, two experiments were conducted in which a broad spectrum MMP inhibitor (FN-439) or artificial cerebrospinal fluid (aCSF) were infused intracerebroventricularly (ICV) under chronic or acute conditions. FN-439 is a well characterized compound that has repeatedly been shown to attenuate the effects of MMPs on the ECM and reduce various indices of (and the underlying process that contribute to) associative and non-associative learning (Brown et al., 2007; Brown, Wilson, Cocking, & Sorg, 2009; Meighan et al., 2006; Wiediger & Wright, 2009; Wright et al., 2007), without producing non-specific effects on behavior (e.g., see Brown et al., 2009).
