Morphological and intracellular signaling changes in response to chronic ethanol and drugs of abuse have been identified (Nestler, 1993; e.g., Ortiz et al., 1995). Extracellular matrix (ECM) proteins provide structural support in the nervous system and in order for synaptic plasticity (e.g., Hebbian, homeostatic and metaplasticity) to occur, the extracellular matrix must be degraded (Dityatev & Fellin, 2008; Lee, Tsang, & Birch, 2008; Wright & Harding, 2004; Wright & Harding, 2009). Furthermore, the ECM is involved in the regulation of intracellular / extracellular signaling, receptor localization in a number of neurotransmitter systems and astrocytic functions (Dityatev et al., 2008). Matrix metalloproteinases (MMPs), a family of proteolytic enzymes, can cleave extracellular matrix proteins to allow for the reconfiguration of neural pathways (Ethell & Ethell, 2007; Lee et al., 2008; Wright et al., 2004). MMP secretion can be stimulated by growth factors and ECM-intracellular signaling pathways (Wright et al., 2009). MMP expression appears to be required for hippocampal-based learning and inhibition of MMPs interferes with induction and maintenance of long-term potentiation, as well as memory tasks (Meighan, Meighan, Davis, Wright, & Harding, 2007; Meighan et al., 2006; Nagy, Bozdagi, & Huntley, 2007; Wright, Brown, & Harding, 2007).
