Dopaminergic regulation of serotonin release in the substantia nigra of the freely moving rat using microdialysis.
The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat substantia nigra (SN) was investigated using in vivo microdialysis. A D1- and D2-receptor-mediated inhibition of nigral 5-HT release was demonstrated in this study. Continuous administration of the D1-receptor agonist CY 208243 (10 microM) through the probe did not alter extracellular DA nor 5-HT from the SN, whereas intranigral administration of the D1-receptor antagonist SCH-23390 HCl (10 microM) significantly increased both DA (to 214%) and 5-HT release (to 168%) from the SN. Co-perfusion of the D1-receptor agonist and antagonist did not change nigral DA nor 5-HT release compared to perfusion of the antagonist alone. The continuous intranigral perfusion of the D2-receptor agonist, (-)-quinpirole HCl (1 microM) significantly decreased both DA ad 5-HT release to 71% and 78%, respectively. These decreases were abolished when the D2-receptor antagonist S(-)-sulpiride (10 microM) and the D2-receptor agonist (-)-quinpirole HCl (1 microM) were co-perfused. In contrast, the intranigral perfusion of the DA precursor, L-DOPA (5 microM; 1 h), significantly increased nigral and striatal 5-HT release to 202% and 155%, respectively. This enhanced nigral 5-HT release might not be receptor-mediated. The results of the present study suggest a D1 and D2 regulation of nigral 5-HT release, either directly mediated by DA receptors on nigral 5-HT terminals or indirectly by nigral GABA, Glu or Asp. Alternatively, the observed DA-5HT-interaction in the SN might not reflect a local interaction but might involve an interaction at the level of the serotonin cell body region, the dorsal raphe nuclei (DRN).
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussels, Belgium.
K
K
Thorré
S
S
Sarre
I
I
Smolders
G
G
Ebinger
Y
Y
Michotte
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin; D007980:Levodopa; D013469:Sulpiride