Research articleFunctional neuroimaging of amphetamine-induced striatal neurotoxicity in the pleiotrophin knockout mouse model

•PTN-/- mice shows decreased metabolism in the striatum & PFC after AMPH compared to WT mice.•Striatal TH loss caused by amphetamine correlates with decreased striatal [18F]-FDG uptake.•[18F]-FDG PET is useful for evaluating AMPH-induced damage in vivo in the brain in mice.•PET overcomes the limitations of more traditional approaches by allowing longitudinal studies.•PET technique makes possible to study the brain in reduced number of animals.

Amphetamine-induced neurotoxic effects have traditionally been studied using immunohistochemistry and other post-mortem techniques, which have proven invaluable for the definition of amphetamine-induced dopaminergic damage in the nigrostriatal pathway. However, these approaches are limited in that they require large numbers of animals and do not provide the temporal data that can be collected in longitudinal studies using functional neuroimaging techniques. Unfortunately, functional imaging studies in rodent models of drug-induced neurotoxicity are lacking. The aim of this study was to evaluate in vivo the changes in brain glucose metabolism caused by amphetamine in the pleiotrophin knockout mouse (PTN-/-), a genetic model with increased vulnerability to amphetamine-induced neurotoxic effects. We showed that administration of amphetamine causes a significantly greater loss of striatal tyrosine hydroxylase content in PTN-/- mice than in wild-type (WT) mice. In addition, [18F]-FDG-PET shows that amphetamine produces a significant decrease in glucose metabolism in the striatum and prefrontal cortex in the PTN-/- mice, compared to WT mice. These findings suggest that [18F]-FDG uptake measured by PET is useful for detecting amphetamine-induced changes in glucose metabolism in vivo in specific brain areas, including the striatum, a key feature of amphetamine-induced neurotoxicity.