INCREASED STRIATAL PROENKEPHALIN MESSENGER-RNA SUBSEQUENT TO PRODUCTION OF SPREADING DEPRESSION IN RAT CEREBRAL-CORTEX - ACTIVATION OF CORTICOSTRIATAL PATHWAYS

Cortical Spreading Depression (CSD) is a slowly propagating wave of de polarization and negative interstitial DC potential, that when induced in the rat brain extends across the entire homolateral hemisphere. De spite evidence that CSD does not penetrate into subcortical regions, n eurochemical changes in areas anatomically connected to cortex have be en reported. In this study in situ hybridization histochemistry was us ed to examine the levels of cholecystokinin (CCK), proenkephalin (ENK) and prodynorphin (DYN) mRNA in cortex and forebrain basal ganglia fol lowing KCl-induced CSD. Unilateral CSD was induced by topical applicat ion of 3 M KCl (similar to 10 mu l) onto the right parietal cortex for 10 min and rats were then killed 1-6 h and 1-28 days later. CCK mRNA levels were increased (P < 0.01) in the ipsilateral neocortex 3 h afte r CSD (13% above levels in contralateral side), reached a peak at 2 da ys (similar to 70%) and were still elevated at 7 (30%) but not, 14 or 28 days later. Unilateral CSD also produced a rapid and sustained incr ease (P < 0.05) in ENK mRNA in ipsilateral piriform cortex (from 3 h t o 2 days; 70-250% above contralateral), and a delayed increase in caud ate putamen and olfactory tubercle at 1 and 2 days (similar to 25% in both regions), but levels were again equivalent to control at 7 days a nd beyond. In contrast, no marked changes in neocortical ENK mRNA, or DYN mRNA in both cortex and basal ganglia, were observed under these c onditions. These findings demonstrate that CSD has specific, rapid and long-lasting effects on neuropeptide expression in neocortex and subc ortical areas. CSD-induced changes in mesostriatal ENK mRNA are propos ed to reflect synaptic activation of local neurons via cortical affere nt projections. (C) 1998 Elsevier Science B.V. All rights reserved.