PROTEIN-KINASE-A AND PROTEIN-KINASE-C ARE INVOLVED IN THE MECHANISMS UNDERLYING CONSOLIDATION OF COCAINE PLACE CONDITIONING

Using a balanced conditioned place preference (CPP) paradigm, we studi ed the role of protein kinases A (PKA) and C (PKC) on the acquisition, consolidation and expression of cocaine place conditioning. H7, a non -selective inhibitor of protein kinases, was administered intracerebro ventricularly at 1 and 10 mu g/10 mu l. The higher dose significantly reduced the time spent by rats in the cocaine compartment when given i mmediately after each conditioning session (consolidation), whereas it had no effect when administered before cocaine during the training ph ase (acquisition) or before testing for place preference in the absenc e of cocaine (expression). The same effect was found on administering immediately after each training session 3 mu g/10 mu l chelerythrine, a selective PKC inhibitor, or 10 mu g/10 mu l H89, a selective PKA inh ibitor, suggesting that both kinases contribute to the consolidation o f stimulus-reward association which determines rats' behavior in the c ocaine CPP. Changes in the activity of PKA and PKC may thus be part of the cascade of events that contribute to enhancing synaptic responses in the consolidation phase of cocaine CPP and determine rats' behavio r associated with the memory of the rewarding effect of cocaine during cocaine CPP expression. These findings may have implications for the study of cocaine 'craving' and relapse. (C) 1997 Elsevier Science B.V.