Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia.

BACKGROUND: Schizophrenia is a disease diagnosed by visible signs and symptoms from late adolescence to early adulthood. The etiology of this disease remains unknown. An objective diagnostic approach is required. Here, we used a mouse model that shows schizophrenia-like phenotypes to study brain glucose metabolism and presynaptic dopaminergic functioning by positron emission tomography (PET) and immunohistochemistry. PET scannings were performed on mice after the administration of [(18)F]-FDG or [(18)F]-F-DOPA. Glucose metabolism was evaluated in basal conditions and after the induction of a hyperdopaminergic state. RESULTS: Mutant animals show reduced glucose metabolism in prefrontal cortex, amygdala, and nucleus reuniens under the hyperdopaminergic state. They also show reduced [(18)F]-F-DOPA uptake in prefrontal cortex, substantia nigra reticulata, raphe nucleus, and ventral striatum but increased [(18)F]-F-DOPA uptake in dorsal striatum. Mutant animals also show reduced tyrosine hydroxylase expression on midbrain neurons. CONCLUSIONS: Dopamine D2 mutant animals show reduced glucose metabolism and impaired presynaptic dopaminergic functioning, in line with reports from human studies. This mouse line may be a valuable model of schizophrenia, useful to test novel tracers for PET scanning diagnostic.