Classification of H2O2 as a Neuromodulator that Regulates Striatal Dopamine Release on a Subsecond Time Scale

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• 作者：Jyoti C. Patel ; Margaret E. Rice
• 刊名：ACS Chemical Neuroscience
• 出版年：2012
• 出版时间：December 19, 2012
• 年：2012
• 卷：3
• 期：12
• 页码：991-1001
• 全文大小：551K
• 年卷期：v.3,no.12(December 19, 2012)
• ISSN：1948-7193

文摘

Here we review evidence that the reactive oxygen species, hydrogen peroxide (H₂O₂), meets the criteria for classification as a neuromodulator through its effects on striatal dopamine (DA) release. This evidence was obtained using fast-scan cyclic voltammetry to detect evoked DA release in striatal slices, along with whole-cell and fluorescence imaging to monitor cellular activity and H₂O₂ generation in striatal medium spiny neurons (MSNs). The data show that (1) exogenous H₂O₂ suppresses DA release in dorsal striatum and nucleus accumbens shell and the same effect is seen with elevation of endogenous H₂O₂ levels; (2) H₂O₂ is generated downstream from glutamatergic AMPA receptor activation in MSNs, but not DA axons; (3) generation of modulatory H₂O₂ is activity dependent; (4) H₂O₂ generated in MSNs diffuses to DA axons to cause transient DA release suppression by activating ATP-sensitive K⁺ (K_ATP) channels on DA axons; and (5) the amplitude of H₂O₂-dependent inhibition of DA release is attenuated by enzymatic degradation of H₂O₂, but the subsecond time course is determined by H₂O₂ diffusion rate and/or K_ATP-channel kinetics. In the dorsal striatum, neuromodulatory H₂O₂ is an intermediate in the regulation of DA release by the classical neurotransmitters glutamate and GABA, as well as other neuromodulators, including cannabinoids. However, modulatory actions of H₂O₂ occur in other regions and cell types, as well, consistent with the widespread expression of K_ATP and other H₂O₂-sensitive channels throughout the CNS.

Keywords:

Brain slices; dorsal striatum; fast-scan cyclic voltammetry; fluorescence imaging; transmitter release; review