The current study prevented synaptic plasticity from occurring in the brain by disabling the molecular mechanisms which allow for ECM degradation and evaluated the consequences of such actions on escalated operant self-administration patterns that are observed during acute withdrawal in dependent rats. MMPs are required for the degradation of the ECM which accompanies plasticity, and so by inhibiting MMPs via FN-439, the ECM is essentially locked in place and plasticity may not occur (Wright and Harding, 2009). In the chronic exposure experiment, the MMP inhibitor FN-439, or aCSF, were chronically administered during the entire dependence induction period and during acute withdrawal operant self-administration sessions. This experiment was designed to broadly block synaptic plasticity associated with both dependence induction and escalated response patterns during acute withdrawal in dependent animals. The results showed that the animals chronically treated with FN-439 did not escalate as the aCSF-treated animals did. These initial findings confirmed that MMPs do have a role in dependence-like phenotypes. However, because the chronic FN-439 treatment spanned both the dependence induction period and post-dependence testing, these initial results did not distinguish
