Dopaminergic regulation of the serotonergic raphe-striatal pathway: microdialysis studies in freely moving rats.

Morphological evidence demonstrates the existence of dopaminergic afferent pathways and dopamine (DA)-containing neurons in the dorsal raphe nucleus (DRN). In a recent report, a DA D2-like receptor-mediated regulation of serotonin (5-HT) extracellular concentration in DRN has been found. Given the existence of somatodendritic 5-HT1A autoreceptors in the DRN, changes of the extracellular concentration of 5-HT in the vicinity of cell bodies and dendrites may be relevant for the control of the activity of ascending serotonergic pathways. In the present brain microdialysis study we have used a chromatographic method (HPLC) enabling the simultaneous measurement of DA, 5-HT, and their main metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA). The presence of a neuronal pool of DA within the DRN was revealed by the local infusion of amphetamine (10 microM), which significantly increased the extracellular concentration of both amines. The local striatal infusion (10 microM) of the selective DA D1-like agonist SKF-38393, the selective DA D2-like agonist quinpirole (LY 171,555), or the nonselective DA agonist apomorphine markedly decreased DA and DOPAC extracellular concentrations and failed to modify 5-HT or 5-HIAA in the striatum, indicating the lack of terminal (striatal) control of 5-HT release by dopaminergic transmission. In contrast, the systemic administration of apomorphine (2.8 mumol/kg, s.c.) significantly increased the extracellular concentration of 5-HT in the DRN and decreased it in the striatum. The reduction of striatal 5-HT extracellular concentration was prevented by the previous administration of the selective 5-HT1A receptor antagonist WAY 100135 (17.6 mumol/kg, s.c.), which by itself did not change extracellular 5-HT in striatum.(ABSTRACT TRUNCATED AT 250 WORDS)