Protein kinases A and C are involved in the mechanisms underlying consolidation of cocaine place conditioning.
Using a balanced conditioned place preference (CPP) paradigm, we studied 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 intracerebroventricularly at 1 and 10 micrograms/10 microliters. The higher dose significantly reduced the time spent by rats in the cocaine compartment when given immediately after each conditioning session (consolidation), whereas it had no effect when administered before cocaine during the training phase (acquisition) or before testing for place preference in the absence of cocaine (expression). The same effect was found on administering immediately after each training session 3 micrograms/10 microliters chelerythrine, a selective PKC inhibitor, or 10 micrograms/10 microliters H89, a selective PKA inhibitor, suggesting that both kinases contribute to the consolidation of stimulus-reward association which determines rats' behavior in the cocaine 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' behavior 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.
Cervo
L
L
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Mukherjee
S
S
Bertaglia
A
A
Samanin
R
R
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009294:Narcotics; D010617:Phenanthridines; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C016299:chelerythrine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D003042:Cocaine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide