Rotenone produces opposite effects upon mouse striatal dopamine function as a result of environmental temperature

Rotenone is a commonly used pesticide that can function as an environmental neurotoxin. Rotenone is a known mitochondrial complex I inhibitor which can lead to oxidative stress and results in dopaminergic cell death. Another environmental factor known to exacerbate oxidative stress and result in striatal dopaminergic cell death is elevated environmental temperature. In this study we evaluated the effects of a single injection of various doses of rotenone (0.65, 1.3 and 2.6 mg/kg) on striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in CD-1 mice and compared this with a single injection of two doses of methamphetamine (MA - 10 or 20 mg/kg), a known striatal DA depleting agent, as administered to mice maintained at 21 degrees C (Experiment 1). These results were then compared to striatal DA and DOPAC concentrations of mice treated with rotenone (1.3 or 2.6 mg/kg) or MA (10 or 20 mg/kg) administered to mice maintained at 28 degrees C (Experiment 2). A single injection of rotenone to mice maintained at 21 degrees C resulted in a significant increase in DA and decrease in DOPAC concentrations for all doses tested compared to controls, whereas a single injection of MA at the same temperature resulted in a significant decrease in DA and no change in DOPAC concentrations. At a temperature of 28 degrees C, a single injection of rotenone resulted in a significant decrease in both DA and DOPAC concentrations similar to that seen with the MA-treated mice. Collectively, these results indicate that rotenone interacts with environmental temperature to produce opposite effects upon striatal DA concentrations -- significantly increasing striatal DA when administered at 21 degrees C and significantly decreasing striatal DA when administered at 28 degrees C, while producing similar decreases in striatal DOPAC under both temperatures.