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.
Brown
Travis E
TE
Department of Veterinary and Comparative Anatomy, Physiology and Pharmacology, Washington State University, Pullman, Washington 99164, USA.
Forquer
Melissa R
MR
Harding
Joseph W
JW
Wright
John W
JW
Sorg
Barbara A
BA
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D020780:Matrix Metalloproteinase 9; D003042:Cocaine