Interaction of the dopaminergic and serotonergic systems in the rat striatum: effects of selective antagonists and uptake inhibitors.

The effects of some selective dopamine (DA) and 5-hydroxytryptamine (5-HT) antagonists and uptake inhibitors on the outflow of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum were studied using microdialysis in conscious rats. Eticlopride (D2 antagonist, 2.5 mg/kg) increased HVA but decreased 5-HIAA, while nomifensine (DA uptake inhibitor, 10 mg/kg) decreased both. Mianserin (5-HT2 antagonist, 2 mg/kg) and citalopram (5-HT uptake inhibitor, 11 mg/kg) also decreased both HVA and 5-HIAA. The selectivity of these drugs and the time course of their effects on HVA and 5-HIAA suggested that the dopaminergic drugs may affect the serotonergic systems primarily via changes in extraneuronal DA and conversely, serotonergic drugs affect the dopaminergic systems via changes in extraneuronal 5-HT. The results obtained are consistent with current evidence that DA and 5-HT release from striatal terminals are regulated by D2 and 5-HT1B autoreceptors, respectively. They also support the idea that, in the rat striatum, presynaptic inhibitory heteroreceptors are a major mechanism that contributes to a reciprocal interaction of the dopaminergic and serotonergic systems.