The Journal of Neurophysiology Vol. 87 No. 2 February 2002, pp. 1155-1158
Copyright ©2002 by the American Physiological Society

RAPID COMMUNICATION

Modulation of Somatodendritic Dopamine Release by Endogenous H₂O₂: Susceptibility in Substantia Nigra But Resistance in VTA

Department of Physiology and Neuroscience and Department of Neurosurgery, New York University School of Medicine, New York, New York 10016

Chen, Billy T., Marat V. Avshalumov, and Margaret E. Rice. Modulation of Somatodendritic Dopamine Release by Endogenous H₂O₂: Susceptibility in Substantia Nigra But Resistance in VTA. J. Neurophysiol. 87: 1155-1158, 2002. We showed previously that dopamine (DA) release in dorsal striatum is inhibited by endogenously generated hydrogen peroxide (H₂O₂). Here, we examined whether endogenous H₂O₂ can also modulate somatodendritic DA release in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), with companion measurements in DA terminal regions. Evoked DA release was monitored in brain slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenous H₂O₂ decreased DA release by 50-60% in SNc and VTA but only by 35% in nucleus accumbens. Whether endogenous H₂O₂ also modulated somatodendritic release was examined using the glutathione peroxidase inhibitor, mercaptosuccinate (MCS), which should increase stimulation-evoked H₂O₂ levels. In the presence of MCS, DA release was suppressed by 30-40% in SNc as well as in dorsal striatum and nucleus accumbens. In striking contrast, DA release in the VTA was unaffected by MCS. These data are consistent with stronger H₂O₂ regulation or lower H₂O₂ generation in VTA than in the other regions. Importantly, oxidative stress has been linked causally to Parkinson's disease, in which DA cells in SNc degenerate, but VTA cells are spared. The present data suggest that differences in oxidant regulation or generation between SNc and VTA could contribute to this.