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.
Wong
P T
PT
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore.
Feng
H
H
Teo
W L
WL
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008803:Mianserin / Q000494:pharmacology; D017551:Microdialysis; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D012457:Salicylamides / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D018492:Dopamine Antagonists; D012457:Salicylamides; D012702:Serotonin Antagonists; D009627:Nomifensine; D008803:Mianserin; D006897:Hydroxyindoleacetic Acid; C045989:eticlopride; D006719:Homovanillic Acid