? The rapid, subsecond signaling of the neurotransmitter dopamine (DA) and neurons in the nucleus accumbens (Acb) have been strongly implicated in cocaine seeking behaviors and drug taking in general. This Career Development Award will characterize the innate responses of DA and Acb cell firing to natural stimuli and how the responses change as a function of learning, motivation and endogenous peptide action. The award will also serve to train the PI in state-of-the-art electrophysiological and electrochemical techniques while he establishes his own independent line of research. In Experiements 1-3, DA and Acb activity will be rapidly sampled in two groups of animals using: 1) in vivo fast-scan cyclic voltammetry at carbon-fiber micrelectrodes (to measure subsecond increases in extracellular Acb DA) and 2) using chronically implanted microwire electrode arrays (to measure the electrophysiological activity of Acb neurons). In Experiement 1, the rapid responses of this system to rewarding (sucrose) and aversive (quinine) taste stimuli will be assessed in naive, untrained rats. In Experiment 2, the role of this system in learning cue-tastant associations will be determined by assaying it before, during and after classical conditioning of environmental stimuli to rewarding (sucrose) or aversive (quinine) tastant delivery. In Experiment 3, the integration of motivated state by this neural system will be assessed by recording rapid responses to the taste of a hypertonic sodium solution in rats with (rewarding) or without (aversive) a sodium appetite. In Experiment 4, the impact of peptides that affect food intake (leptin, melancortins) on rapid DA signaling in the Acb will be determined in an in vitro brain slice preparation. Effects of these peptides on rapid DA release would strongly support investigation of the use of these peptides not just in the treatment of obesity but in the treatment of drug addiction as well. These studies will establish the range of natural stimuli that promote rapid DA-Acb signaling - setting the foundation for examining aberrant signaling underlying drug addiction. ? ? ? ?
| Roitman, Jamie D; Roitman, Mitchell F (2010) Risk-preference differentiates orbitofrontal cortex responses to freely chosen reward outcomes. Eur J Neurosci 31:1492-500 |
| Roitman, Mitchell F; Wheeler, Robert A; Wightman, R Mark et al. (2008) Real-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuli. Nat Neurosci 11:1376-7 |
| Day, Jeremy J; Roitman, Mitchell F; Wightman, R Mark et al. (2007) Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbens. Nat Neurosci 10:1020-8 |
