Exposure to a mild stressor can often precondition cells such that they are less sensitive to a more intense stress of the same or different type. Although most of this work has involved ischemic preconditioning, we have recently shown that preconditioning also can be seen as a result of mild oxidative stress in a cellular model of Parkinson’s disease (see Leak et al., SFN, 2005). In this report, we further extend our observations to include the use of methamphetamine (METH) as a preconditioning stimulus. METH acts by releasing dopamine (DA) from vesicles, inhibiting monoamine oxidase, and reversing high affinity DA transport across cell membranes. For these studies we used the dopaminergic cell line MN9D cultured in the presence of serum, measuring cellular viability with an assay for ATP. We first observed that exposure of MN9D cells to METH (5 mM) for 24 hr caused a large reduction in cellular viability (-89%). Next, MN9D cells were exposed to 6-hydroxydopamine (6-OHDA), a neurotoxin that is accumulated...