INHIBITION OF PROTEIN-KINASE-C, BUT NOT OF PROTEIN-KINASE-A, BLOCKS THE DEVELOPMENT OF ACUTE ANTINOCICEPTIVE TOLERANCE TO AN INTRATHECALLY ADMINISTERED MU-OPIOID RECEPTOR AGONIST IN THE MOUSE

A specific protein kinase C inhibitor, calphostin C, which injected al one had no effect on the antinociception induced by intrathecal (i.t.) administration of a selective mu-opioid receptor agonist, [D-Ala(2),N MePhe(4),Gly(ol)5]enkephalin (DAMGO), dose-dependently attenuated the development of acute tolerance to the i.t. DAMGO-induced antinocicepti on in male ICR mice. On the other hand, a selective protein kinase A i nhibitor, KT5720, did not have any effect on the development of acute tolerance to DAMGO antinociception. These findings suggest that protei n kinase C, but not protein kinase A, plays an important role in the d evelopment of acute tolerance to the mu-opioid receptor agonist-induce d antinociception.