Increase in matrix metalloproteinase-9 levels in the rat medial prefrontal cortex after cocaine reinstatement of conditioned place preference

Recently we have shown that inhibition of matrix metalloproteinase (MMP) activity suppresses the reinstatement of cocaine‐primed conditioned place preference (CPP) in rats. Here we explored whether cocaine‐primed reinstatement was associated with increased activity of the gelatinases, MMP‐2 or MMP‐9, in the medial prefrontal cortex (mPFC) or dorsal hippocampus. Male Sprague‐Dawley rats underwent training for cocaine‐CPP followed by extinction sessions and either saline‐ or cocaine‐priming injections. Cocaine‐induced reinstatement produced significant increases in mPFC MMP‐9 activity at 1, 3 and 24 hr after injection compared with saline controls. No changes in MMP‐9 occurred in the hippocampus or in MMP‐2 activity in either brain region. Also, no changes in mPFC MMP‐9 activity were observed 1 hr after reinstatement in animals given no extinction sessions but equivalent time off in the home cage. Finally, MMP‐3 protein levels were not different in either brain region at any of the three time points assessed. These results suggest that an elevation in MMP‐9 activity in the mPFC may contribute to synaptic remodeling important for the reactivation of a cocaine memory, or alternatively, for the modification of a competing extinction memory during reinstatement. Synapse 62:886–889, 2008. © 2008 Wiley‐Liss, Inc.