The effects of acute and repeated cocaine injections on protein kinase C activity and isoform levels in dopaminergic brain regions.

The present study was designed to assess the effects of acute and repeated cocaine exposure on protein kinase C (PKC) activity and the levels of calcium-dependent isoforms of PKC in mesocorticolimbic and nigrostriatal dopamine brain regions. Animals received repeated injections of saline or cocaine and were challenged with saline or cocaine 24 h or 7 days after the last of their daily injections. Animals were sacrificed 2, 6 or 24 h after the challenge injection and their brains were dissected and used in PKC studies. The data demonstrated that previously reported cocaine-induced increases in PKC activity in the ventral tegmental area are transient and not associated with changes in the levels of calcium-dependent isoforms of PKC. In addition, there was a decrease in membrane-associated PKC activity, with a concomitant increase in the levels of PKCbetaI in the medial prefrontal cortex 24 h after the last injection of cocaine. These data suggest that changes in PKC activity in the ventral tegmental area may be involved in the initiation of sensitization whereas changes in PKC activity in the medial prefrontal cortex may be related to the expression of the sensitized response to cocaine.