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 repe ated cocaine exposure on protein kinase C (PKC) activity and the level s of calcium-dependent isoforms of PKC in mesocorticolimbic and nigros triatal dopamine brain regions. Animals received repeated injections o f saline or cocaine and were challenged with saline or cocaine 24 h or 7 days after the last of their daily injections. Animals were sacrifi ced 2, 6 or 24 h after the challenge injection and their brains were d issected and used in PKC studies. The data demonstrated that previousl y reported cocaine-induced increases in PKC activity in the ventral te gmental area are transient and not associated with changes in the leve ls of calcium-dependent isoforms of PKC. In addition, there was a decr ease in membrane-associated PKC activity, with a concomitant increase in the levels of PKC beta(1) in the medial prefrontal cortex 24 h afte r the last injection of cocaine. These data suggest that changes in PK C activity in the ventral tegmental area may be involved in the initia tion of sensitization whereas changes in PKC: activity in the medial p refrontal cortex may be related to the expression of the sensitized re sponse to cocaine. (C) 1998 Elsevier Science Ireland Ltd. All rights r eserved.