Rapid DA-Acb signaling in ingestive behaviors
Principal Investigator: MITCHELL ROITMAN
Abstract: [unreadable] DESCRIPTION (provided by applicant): [unreadable] 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. [unreadable] [unreadable] [unreadable] [unreadable]
Funding Period: 2004-09-10 - 2009-06-30
more information: NIH RePORT
- Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbensJeremy J Day
Department of Psychology, Davie Hall CB no 3270, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Nat Neurosci 10:1020-8. 2007..Consistent with proposed roles in reward prediction and incentive salience, these results indicate that rapid dopamine release provides a reward signal that is dynamically modified by associative learning...
- Real-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuliMitchell F Roitman
Department of Psychology, University of Illinois, Chicago, Illinois 60607, USA
Nat Neurosci 11:1376-7. 2008..This rapid encoding may serve to guide ongoing behavioral responses and promote plastic changes in underlying circuitry...
- Risk-preference differentiates orbitofrontal cortex responses to freely chosen reward outcomesJamie D Roitman
Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA
Eur J Neurosci 31:1492-500. 2010..Such enhanced neural responding to risky rewards may serve to bias individuals towards risk-preference in decision-making...