Although the present experiments evaluated chronic FN-439 during dependence induction and acute withdrawal testing or during acute withdrawal test sessions only, we did not directly focus on inhibition of MMPs exclusively during the dependence induction period and the fact that the neuroadaptations that occur during that time period potentially serve as necessary prerequisites for typical escalated responding observed during acute withdrawal in dependent animals. Future studies will be needed to systematically investigate the precise changes produced by ethanol dependence and determine the role of MMPs in the dependence-induced neuroadaptations and plasticity.
