Repeated administration of psychostimulant drugs such as cocaine and amphetamine produces long lasting neuroadaptations in the brain, including alterations in dendritic branching and spine density of medium spiny neurons of the nucleus accumbens (Acb) and pyramidal neurons of the medial prefrontal cortex (MPC). The overall aim of the application is to develop and apply viral expression technology with confocal microscopy to visualize and characterize drug-induced alterations of neuronal morphology. First, green fluorescent protein (GFP) will be virally overexpressed in vivo in order to visualize dendritic branches and spines in Acb and MPC of rats. Second, viral-mediated gene transfer will be employed, as an alternative to Golgi staining, to determine whether repeated exposure to amphetamine or cocaine produces morphological changes in neurons of the striatum and MPC. Third, in order to examine whether psychostimulant induced structural plasticity involve alterations in synaptic protein distribution in these brain regions, different fusion proteins such as actin or PSD-95 conjugated to GFP will be expressed. The proposed experiments will provide important new insights into the mechanisms underlying drug-experience dependent plasticity in the brain.
