Intra-hippocampal inhibition of protein kinase AII attenuates morphine-induced conditioned place preference.
Morphine and other drugs of abuse modulate protein kinase A (PKA) signaling within the mesolimbic reward pathway. Using a balanced conditioned place preference (CPP) paradigm, we studied the possible involvement of protein kinase AII (PKA II) on the acquisition, expression and consolidation of morphine place conditioning in male Wistar rats. Subcutaneous administration of various doses of morphine sulfate (1-9 mg/kg) induced CPP in a dose-dependent manner. H-89, a selective PKA II inhibitor, was administered into CA1 region of the hippocampus at 1, 2.5 and 5 microM/rat. Using a 3-day schedule of conditioning, it was found that the H-89 did not produce a significant place preference or place aversion. H-89 (1, 2.5 and 5 microM/rat) significantly reduced the time spent by rats in the morphine compartment when given immediately after each conditioning session (consolidation), whereas it had no effect when administered before morphine during the conditioning phase (acquisition) or before testing for place preference in the absence of morphine (expression). It is concluded that the PKA II may play an active role in the consolidation of reward-related memory of morphine in CA1 region of the hippocampus.
Sharifzadeh
Mohammad
M
Department of Pharmacology and Toxicology, Medicinal Plants and Pharmaceutical Sciences Research Centers, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. msharifzadeh@sina.tums.ac.ir
Haghighat
Atieh
A
Tahsili-Fahadan
Pouya
P
Khalaj
Siavash
S
Zarrindast
Mohammad-Reza
MR
Zamanian
Ali-Reza
AR
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D007546:Isoquinolines; D009294:Narcotics; D013449:Sulfonamides; D009020:Morphine; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide