enhances ethanol reward (Bahi and Dreyer, 2012). Withdrawal seizures are reduced in tPA-deficient mice following chronic ethanol administration (Pawlak et al., 2005). Inhibition of proteolytic enzymes that degrade the ECM block escalated responding during acute withdrawal in dependent animals (Smith et al., 2011). Collectively, these results argue that ECM structural components (like COL6A3) and remodeling enzymes are important determinants of ethanol-induced neuroadaptation. We hypothesize that Col6a3 may underlie the Alcw5 HIC QTL.
