Age differences in sensitivity to H 2O 2- or no-induced reductions in K +-evoked dopamine release from superfused striatal slices: Reversals by PBN or Trolox

Abstract

Previous research has indicated that many age-related functional alterations may be the result of a decreased ability of the organism to respond to oxidative stress (OS). However, this hypothesis is based on indirect indices of function (e.g., increased vulnerability of hepatocytes from senescent animals to H 2O 2-induced DNA damage, increases in lipofuscin accumulation). More direct tests of this hypothesis, especially as it relates to brain aging, have not been extensively undertaken. Present experiments were carried out to make such tests by examining age differences in the sensitivity to OS on reductions in striatal dopamine (DA) release. Thus, K +-evoked DA (K +-ERDA) release from superfused striatal slices from young (6–8 month) and old (24–25 month) animals was examined following either: (a) application of the NO-generator sodium nitroprusside or (b) preincubation with H 2O 2. In order to assess the specific effects of OS on muscarinic (mAChR) sensitivity, oxotremorine-enhancement of K +-ERDA was examined following incubation with H 2O 2. Results showed that the striatal tissue from the old animals showed greater sensitivity to both H 2O 2 and NO than young animals, and stimulated DA decreased at lower concentrations of these agents (e.g., NO—100 μM young, 30 μM old). In addition, H 2O 2 was also effective in reducing oxo-enhanced K +-ERDA and was more effective as a function of age. If the striatal tissue was incubated in either Trolox (α-tocopherol) or α-phenyl- n-tert-butyl nitrone (PBN) prior to OS, the negative effects of NO · and H 2O 2 were reversed in both age groups. Results are discussed in terms of age-related membrane and endogenous antioxidant alterations that could induce increases in sensitivity to OS and the specificity of antioxidants in reducing this sensitivity in key functional systems.