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Metabolite studies of methamphetamine effects based upon mitochondrial respiratiory state in rat brain.

Methamphetamine-induced changes in metabolite levels were studied based upon a new approach to tissue sampling. In this procedure, the noninvasive, autoindicated redox state of intramitochondrial NADH was used to determine the point at which samples were taken rather than the time after drug injection. By this combination of in situ microfluorometry and tissue assay, a complex sequence of rapid changes in cerebral intermediary metabolism and associated mitochondrial redox shifts were observed. These changes were found to occur over a wide range of time course among animals after drug administration, and this temporal variation in response to the drug may be the factor for previously reported inconsistencies in metabolite patterns after methamphetamine. This finding emphasizes the potential difficulties that temporal variability produces in certain cerebral pharmacological responses and the value of the noninvasive, autoindicated redox keyed technique (NARK analysis) for metabolite sampling.