@article{spanos_xie_gras-najjar_white_sombers_2018, title={NMDA Receptor-Dependent Cholinergic Modulation of Mesolimbic Dopamine Cell Bodies: Neurochemical and Behavioral Studies}, volume={10}, ISSN={1948-7193 1948-7193}, url={http://dx.doi.org/10.1021/acschemneuro.8b00492}, DOI={10.1021/acschemneuro.8b00492}, abstractNote={Substance abuse disorders are devastating, costly, and difficult to treat. Identifying the neurochemical mechanisms underlying reinforcement promises to provide critical information in the development of effective treatments. Several lines of evidence suggest that striatal dopamine (DA) release serves as a teaching signal in reinforcement learning, and that shifts in DA release from the primary reward to reward-predicting stimuli play a critical role in the self-administration of both natural and non-natural rewards. However, far less is known about the reinforcing effects of motivationally neutral sensory stimuli, or how these signals can facilitate self-administration behavior. Thus, we trained rats ( n = 7) to perform a visual stimulus-induced instrumental task, which involved lever pressing for activation of a stimulus light. We then microinfused vehicle (phosphate buffered saline), carbachol (acetylcholine receptor agonist), or carbachol in the presence of an N-methyl-d-aspartate (NMDA) receptor-specific drug (NMDA itself, or the antagonist, AP5) into the ventral tegmental area (VTA). This enabled us to directly evaluate how chemical modulation of dopamine cell bodies affects the instrumental behavior, as well as the nature of extracellular dopamine transients recorded in the nucleus accumbens shell (NAc shell) using fast-scan cyclic voltammetry (FSCV). Intra-VTA infusion of carbachol enhanced the magnitude and frequency of dopamine transients in the NAc shell and potentiated active lever responding without altering inactive lever responding, as compared to infusion of vehicle. Coinfusion of carbachol with AP5 abolished dopamine transients recorded in the NAc and attenuated active lever responding without altering inactive lever responding. Finally, coadministration of carbachol and NMDA into the VTA restored both lever pressing and dopaminergic signals recorded in the striatum. Together, these results suggest that acetylcholine and glutamate synergistically act at dopamine cells in the VTA to modulate VTA-NAc shell dopaminergic output, and this underlies motivation to lever press for a motivationally neutral visual stimulus.}, number={3}, journal={ACS Chemical Neuroscience}, publisher={American Chemical Society (ACS)}, author={Spanos, Marina and Xie, Xiaohu and Gras-Najjar, Julie and White, Stephanie C. and Sombers, Leslie A.}, year={2018}, month={Nov}, pages={1497–1505} }
 @article{spanos_gras-najjar_letchworth_sanford_toups_sombers_2013, title={Quantitation of Hydrogen Peroxide Fluctuations and Their Modulation of Dopamine Dynamics in the Rat Dorsal Striatum Using Fast-Scan Cyclic Voltammetry}, volume={4}, ISSN={["1948-7193"]}, DOI={10.1021/cn4000499}, abstractNote={The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson's disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson's disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum attenuated electrically evoked DA release, and also decreased basal DA levels in this brain region. These novel results will help to disambiguate the chemical mechanisms underlying the progression of neurodegenerative disease states, such as Parkinson's disease, that involve oxidative stress.}, number={5}, journal={ACS CHEMICAL NEUROSCIENCE}, author={Spanos, Marina and Gras-Najjar, Julie and Letchworth, Jeremy M. and Sanford, Audrey L. and Toups, J. Vincent and Sombers, Leslie A.}, year={2013}, month={May}, pages={782–789} }