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).
Thorré
K
K
Department of Pharmaceutical Chemistry and Drug Analysis, Vrije Universiteit Brussels, Belgium.
Sarre
S
S
Smolders
I
I
Ebinger
G
G
Michotte
Y
Y
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