Research in the Rice laboratory is focused on factors that regulate dopamine (DA) release in the brain. DA plays significant roles in motor control, in reward and emotion, and in cognition; conversely, DA pathology has been implicated in movement disorders including Parkinson's disease and dystonia, in substance abuse including addiction to cocaine or amphetamines, and in psychiatric disorders including schizophrenia and depression. Using carbon-fiber microelectrodes with fast-scan cyclic voltammetry, we examine regulation of synaptic dopamine release in two primary axon terminal regions: the dorsal striatum, which is involved in motor control; and the nucleus accumbens, which is involved in reward pathways. We also examine somatodendritic DA release in the DA cell body regions in the substantia nigra and ventral tegmental area. Recently, we have begun to using whole-cell recording to examine DA neuron activity in these cell body regions. Our studies of local regulation of DA release and DA cell activity have revealed that hydrogen peroxide (H2O2), a relatively inert, diffusible reactive oxygen species, is an endogenous regulator of the nigrostriatal DA pathway. In the dorsal striatum, hydrogen peroxide is generated downstream from glutamate receptor activation and inhibits synaptic DA release (Avshalumov et al. 2003; Avshalumov and Rice 2003). In the substantia nigra, DA neurons generate hydrogen peroxide (presumably from mitochondria) during normal cellular activity; peroxide in turn opens ATP-sensitive potassium channel (KATP channels) to inhibit cell firing, thereby providing a novel link between metabolism and cell firing rate (Avshalumov et al. 2005). We have developed a method for imaging hydrogen peroxide in individual neurons using a fluorescent peroxide-sensitive dye to monitor activity-dependent hydrogen peroxide generation (see figure below). In related studies of striatal DA regulation, we examined the role of acetylcholine in the control of DA release via nicotinic receptors; our findings have important implications for addiction to nicotine/smoking (Rice and Cragg 2004).