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 wer e studied using microdialysis in conscious rats. Eticlopride (D-2 anta gonist, 2.5 mg/kg) increased HVA but decreased 5-HIAA, while nomifensi ne (DA uptake inhibitor, 10 mg/kg) decreased both. Mianserin (5-HT2 an tagonist, 2 mg/kg) and citalopram (5-HT uptake inhibitor, 11 mg/kg) al so decreased both HVA and 5-HIAA. The selectivity of these drugs and t he time course of their effects on HVA and 5-HIAA suggested that the d opaminergic drugs may affect the serotonergic systems primarily via ch anges in extraneuronal DA and conversely, serotonergic drugs affect th e 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 D-2 and 5-HT1B autoreceptors , respectively. They also support the idea that, in the rat striatum, presynaptic inhibitory heteroreceptors are a major mechanism that cont ributes to a reciprocal interaction of the dopaminergic and serotonerg ic systems.