We are interested in altered regulation of the central dopamine system in animal models of various neuropsychiatric diseases including schizophrenia, depression, compulsive cocaine abuse and Parkinson's disease. Elucidation of such regulatory changes and their modification by experimental manipulations are expected to help in developing various therapeutic modes for these disorders. Experimental therapeutic modes being evaluated in our laboratory include drug
therapy, gene therapy and direct transplantation of viable cells into the brain. We utilize single-unit recording (extracellular and whole-cell) and fast-scan cyclic voltammetry techniques to examine, in "real-time," regulation of neurotransmission in the nigrostriatal, mesolimbic and mesocortical dopamine pathways. Electrophysiologically (single-unit recording), we characterize alterations in: (1) the baseline activity of single dopamine neurons; and (2) the sensitivity of various neurotransmitter receptors and transporters. In vivo, specific probes are administered systemically or via microiontophoresis/pressure
ejection and responses measured. In slice preparations, drugs are directly bath-applied or via photolysis of caged-compounds. The in vitro experiments are used not only to complement our in vivo studies but also to examine for any changes in the synaptic activities (e.g., neurotransmitter release) controlling dopamine cell activity. We also use fast scan voltammetry technique in order to study changes in the terminal areas of dopamine neurons (cf. single-unit recording technique for studying changes in the cell body regions). This
electrochemical technique allows measurement of synaptic dopamine concentrations every 50-100 msec, thus allowing "real-time" assessment of the dynamic control of dopamine neurotransmission.