Fig. 10.

Changes induced by morphine in the MOR-NMDAR pathway: effect of PKC inhibition and NMDAR antagonism. Control: mice received the priming icv dose of 10 nmol morphine and 24 h later, an identical second dose (test dose). Treatment: Gö7874 and MK-801 (1 nmol) were administered to CD1 mice 24 h after the priming dose of morphine, 30 min before the test dose. Groups of mice were killed at the intervals described and PAG synaptosomes were obtained. MOR regulation: MOR was immunoprecipitated and its serine phosphorylation was determined at specified intervals after the first injection of opioid and also, after the second dose of the opioid. The presence of MOR-associated Gαi2 subunits was determined. NMDAR regulation: The amounts of activating pTyr1325 NR2A and pThr286 CaMKII were directly determined in PAG synaptosomes. The effects of Gö7874 and MK-801 on the changes brought about by the first dose of morphine when studied 24 h after this injection and how they evolved after these treatments in response to the second dose of the opioid are shown on the right