AGE-DIFFERENCES IN SENSITIVITY TO H2O2-INDUCED OR NO-INDUCED REDUCTIONS IN K-EVOKED DOPAMINE RELEASE FROM SUPERFUSED STRIATAL SLICES - REVERSALS BY PBN OR TROLOX()

Previous research has indicated that many age-related functional alter ations may be the result of a decreased ability of the organism to res pond to oxidative stress (OS). However, this hypothesis is based on in direct indices of function (e.g., increased vulnerability of hepatocyt es from senescent animals to H2O2-induced DNA damage, increases in lip ofuscin accumulation). More direct tests of this hypothesis, especiall y as it relates to brain aging, have not been extensively undertaken. Present experiments were carried out to make such tests by examining a ge differences in the sensitivity to OS on reductions in striatal dopa mine (DA) release. Thus, K+- evoked DA (K+-ERDA) release from superfus ed striatal slices from young (6-8 month) and old (24-25 month) animal s was examined following either: (a) application of the NO-generator s odium nitroprusside or (b) preincubation with H2O2. in order to assess the specific effects of OS on muscarinic (mAChR) sensitivity, oxotrem orine-enhancement of K+-ERDA was examined following incubation with H2 O2. Results showed that the striatal tissue from the old animals showe d greater sensitivity to both H2O2 and NO than young animals, and stim ulated DA decreased at lower concentrations of these agents (e.g., NO- 100 mu M young, 30 mu M old). In addition, H2O2 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 (alpha-toco pherol) or alpha-phenyl-n-tert-butyl nitrone (PEN) prior to OS, the ne gative effects of NO. and H2O2 were reversed in both age groups, Resul ts are discussed in terms of age-related membrane and endogenous antio xidant alterations that could induce increases in sensitivity to OS an d the specificity of antioxidants in reducing this sensitivity in key functional systems.