Correlative analysis of dopaminergic and serotonergic metabolism across the brain to study monoaminergic function and interaction.

BACKGROUND: The widespread innervation of dopamine (DA) and serotonin (5-HT) systems in cortical and subcortical regions suggests that their biochemical interactions can occur in multiple regions directly or indirectly via neurobiological networks.

NEW METHOD: The present study was aimed at validating a neurochemical approach of monoaminergic function based on inter-individual variability of monoamine tissue contents in various cortical and subcortical areas. We focused on monoamines metabolism and examined correlations within and between these monoaminergic systems in selected regions for the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) alone or with respect to the turnover indexes DOPAC/DA, DOPAC+HVA/DA and 5-HIAA/5-HT.

RESULTS: The tissue content of metabolites and their parent drug correlated within a brain region. Conversely, a few specific relationships (10%) were observed for each turnover in paired brain regions and even less between the 5-HT and DA turnovers. The number of correlations was lower when looking at the metabolite tissue contents. In all cases, the 5-HT and DA turnover indexes or metabolites correlated positively within a brain region.

COMPARISON WITH EXISTING METHOD(S): These data validate the inter-individual analysis of monoamine tissue content by providing evidence that the metabolite correlates with the parent neurotransmitter in the same region. The pattern of correlations of metabolisms reported here differs from that of the parent neurotransmitters, notably regarding the relationships of DA turnovers between striatal territories.

CONCLUSION: The whole neurochemical approach is of interest for characterizing monoaminergic systems interaction in various genetic or pharmacological models of neuropsychiatric diseases.