The intention of this project is to examine post-synaptic changes in second messenger systems in brain areas involved in behavioral sensitization to cocaine or kindling. The role of dopamine-regulated phosphoproteins (i.e., DARPP-32) in the striatum during behavioral sensitization is being studied. Preliminary results suggest that the increase in the phosphorylation of DARPP-32 seen with acute cocaine administration are attenuated following repeated administration of cocaine. In addition, FOS, a transcription factor that acts as a third messenger, appears to be increased in the striatum following repeated cocaine injection when compared with acute cocaine administration or no cocaine controls. With electrical kindling of the amygdala, long-lasting changes in activity of protein kinases are being investigated. Kinase activity in membrane fractions of hippocampus appears to be increased three weeks after the last kindled seizure. Previous work has already shown that c-fos is increased in discrete regions of brain following kindled seizures.
