K. Thorre et al., DOPAMINERGIC REGULATION OF SEROTONIN RELEASE IN THE SUBSTANTIA-NIGRA OF THE FREELY MOVING RAT USING MICRODIALYSIS, Brain research, 796(1-2), 1998, pp. 107-116
The functional regulation by dopamine (DA) receptors of serotonin (5-H
T) release from the rat substantia nigra (SN) was investigated using i
n vivo microdialysis, A D-1- and D-2-receptor-mediated inhibition of n
igral 5-HT release was demonstrated in this study. Continuous administ
ration of the D-1-receptor agonist CY 208243 (10 mu M) through the pro
be did not alter extracellular DA nor 5-HT from the SN, whereas intran
igral administration of the D-1-receptor antagonist SCH-23390 HCl (10
mu M) significantly increased both DA (to 214%) and 5-HT release (to 1
68%) from the SN. Co-perfusion of the D-1-receptor agonist and antagon
ist did not change nigral DA nor 5-HT release compared to perfusion of
the antagonist alone. The continuous intranigral perfusion of the D-2
-receptor agonist, (-)-quinpirole HCl (1 mu M) significantly decreased
both DA and 5-HT release to 71% and 78%, respectively. These decrease
s were abolished when the D-2-receptor antagonist S(-)-sulpiride (10 m
u M) and the D-2-receptor agonist(-)-quinpirole HCl (1 mu M) were co-p
erfused. In contrast, the intranigral perfusion of the DA precursor, L
-DOPA (5 mu M; 1 h), significantly increased nigral and striatal 5-HT
release to 202% and 155%, respectively. This enhanced nigral 5-HT rele
ase might not be receptor-mediated. The results of the present study s
uggest a D-1 and D-2 regulation of nigral 5-HT release, either directl
y mediated by DA receptors on nigral 5-HT terminals or indirectly by n
igral 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). (C) 1998 Elsevier Science B.V. All rights reserve
d.