[Abstract Title]. - Society for Neuroscience

availability can affect mitochondrial respiration and therefore modulate DA release indirectly via
H2O2. KATP-channel-dependent suppression of evoked DA release in striatal slices was the
primary indicator of changes in modulatory H2O2 generation; H2O2-responsive chloromethyl
dichlorodihydrofluorescein diacetate (CM-H2DCFDA) fluorescence imaging was used to
confirm changes in levels of reactive oxygen species. Striatal ATP content was also determined
after incubating slices in varying glucose concentrations.
Axonal DA release was evoked by either one-pulse or pulse-train stimulation (30 pulses, 10 Hz)
and extracellular DA concentration ([DA]o) was monitored using carbon-fiber microelectrodes
and fast-scan cyclic voltammetry in striatal slices in control (10 mM), low (1 mM), and high (30
mM) glucose media; ionic strength was maintained by NaCl substitution. Inhibition of
glutathione (GSH) peroxidase with mercaptosuccinate (MCS, 1 mM), which amplifies levels of
endogenous H2O2, had no effect on one-pulse evoked [DA]o (n = 7), but suppressed pulse-train
evoked [DA]o by 35% (n = 6) in 10 mM glucose, as previously. Decreasing glucose to 1 mM had
no effect on either one-pulse or pulse-train evoked [DA]o (n = 6-7), despite a significant 14%
decrease in tissue ATP content and increased H2O2 generation (n = 12). However, in 1 mM
glucose, the effect of MCS on pulse-train evoked [DA]o was enhanced to a 55% decrease from
control (n = 6). Elevating glucose to 30 mM did not alter ATP content (n = 29), but suppressed
H2O2 generation. Consequently, H2O2-modulated pulse-train evoked [DA]o was significantly
enhanced in 30 mM glucose (n = 6). Moreover, the usual suppression of pulse-train evoked
[DA]o by MCS was markedly attenuated in 30 mM glucose (n = 7). By contrast, exogenous H2O2
(1.5 mM) produced a 40% decrease in pulse-train evoked [DA]o in 30 mM glucose, indicating
that normal H2O2/KATP-channel dependent inhibition of DA release was intact (n = 6). Overall,
these data show that glucose modulates pulse-train stimulation evoked DA release by altering
H2O2 generation, but not ATP content.
Disclosures: L. Bao , None; C.R. Lee, None; M.E. Rice, None.
Poster
274. Basal Ganglia: Transmitters and Neuromodulation II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 274.6/JJ1
Topic: D.15.a. Transmitters and neuromodulation
Support: NIH/NIDA/IRP
Title: The apparent uniformity of projections to the accumbens and caudate-putamen from the
ventral tegmental area constitutes a composite of merged patches: A different perspective on the
mesostriatal projection