Cocaine: effects on single neurons

PROJECT SUMMARY The role of dopamine in health and disease has been investigated for decades. Dopamine receptor agonists or antagonists are used for the treatment diseases such as schizophrenia, depression, attention deficit disorder and Parkinson's disease. Recent work also indicates that the altered regulation of dopamine release induced by many drugs of abuse play a critical role in early processes linked to early aspects of addiction. Thus knowledge of the physiological role of endogenous dopamine in the central nervous system is necessary. This proposal uses recordings from dopamine neurons of the Substantia Nigra in brain slices from mouse to (1) Identify the distribution of D2 receptors on distinct dendritic projections. (2) Define sites of dopamine release, determine the time course of the presence of dopamine in the extracellular space following synaptic release and the time course of the dopamine/D2- receptor interaction that underlies the inhibitory postsynaptic potential. (3) Characterize plasticity of D2-receptors focusing on heterologous desensitization between GPCRs and the acute application of cocaine. Finally, future experiments will determine how D2-receptor function and distribution are altered following treatment of animals with cocaine. The results of this study will form a connection between D2 receptor dependent synaptic events and the early events following treatment with cocaine. This knowledge will add to the decades long search for an understanding of the role of dopamine in health and disease.