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Animal data suggest that the widely abused psychostimulant methamphetamine can damage brain dopamine neurones by causing dopamine-dependent oxidative stress; however, the relevance to human methamphetamine users is unclear. We measured levels of key antioxidant defences [reduced (GSH) and oxidized (GSSG) glutathione, six major GSH system enzymes, copper­zinc superoxide dismutase (CuZnSOD), uric acid] that are often altered after exposure to oxidative stress, in autopsied brain of human methamphetamine users and matched controls. Changes in the total (n 1/4 20) meth- amphetamine group were limited to the dopamine-rich caudate (the striatal subdivision with the most severe dopamine loss) in which only activity of CuZnSOD (+ 14%) and GSSG levels (+ 58%) were changed. In the six methamphetamine users with severe (- 72 to ) 97%) caudate dopamine loss, caudate CuZnSOD activity (+ 20%) and uric acid levels (+ 63%) were increased with a trend for decreased () 35%) GSH concentration. Our data suggest that brain levels of many antioxidant systems are preserved in methampheta- mine users and that GSH depletion, commonly observed during severe oxidative stress, might occur only with severe dopamine loss. Increased CuZnSOD and uric acid might reflect compensatory responses to oxidative stress. Future studies are necessary to establish whether these changes are associated with oxidative brain damage in human metham- phetamine users. [ABSTRACT FROM AUTHOR]

Objective: Neuroimaging and genetic studies suggest that individual differences in the brain dopaminergic system contribute to the normal variability of human personality (e.g., social detachment and novelty seeking). The authors studied whether presynaptic dopamine function is also associated with personality traits. Method: Presynaptic dopamine synthesis capacity in the brain was measured with positron emission tomography and [[sup 18]F]fluorodopa in 33 healthy adults, and personality traits were assessed with the Karolinska Scales of Personality. Associations were studied by using a linear regression model controlling for the effects of age and gender on both variables. Results: High scores on two of the anxiety-related personality scales, somatic anxiety and muscular tension, and on one aggressivity-related scale, irritability, were significantly associated with Iow [[sup 18]F]fluorodopa uptake in the caudate. No statistically significant associations were observed between [[sup 18]F]fluorodopa uptake and the detachment scale or scales related to novelty-seeking behavior (impulsiveness and monotony avoidance). Conclusions: The results suggest a role for the dopaminergic system in the regulation of anxiety in healthy subjects. Together with previous studies, they also indicate differential involvement of various components of the dopaminergic system in normai and pathological personality traits. [ABSTRACT FROM AUTHOR]