Neurochemical and electrophysiological evidence that 5-HT4 receptors exert a state-dependent facilitatory control in vivo on nigrostriatal, but not mesoaccumbal, dopaminergic function

Guillaume Lucas, Vincenzo Di Matteo, Philippe De Deurwaerdère, Grégory Porras, Raúl Martín-Ruiz, Francesc Artigas, Ennio Esposito, Umberto Spampinato
European Journal of Neuroscience. 2001-03-01; 13(5): 889-898
DOI: 10.1046/j.0953-816X.2000.01453.x

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In this study we investigated, using in vivo microdialysis and single unit
recordings, the role of serotonin4 (5-HT4) receptors in the control of
nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity. In freely
moving rats, the 5-HT4 antagonist GR 125487 (1 mg/kg, i.p.), without effect on
its own, significantly reduced the enhancement of striatal DA outflow induced by
0.01 (-35%) and 0.1 (-66%), but not 1 mg/kg, s.c. haloperidol (HAL).
Intrastriatal infusion of GR 125487 (1 microM) had no influence on basal DA
outflow, but attenuated (-49%) the effect of 0.01 mg/kg HAL. Systemic
administration of GR 125487 modified neither basal nor 0.01 mg/kg HAL-stimulated
accumbal DA outflow. In halothane-anaesthetized rats, 1 or 10 mg/kg GR 125487,
without effect by itself, failed to modify the changes in accumbal and striatal
DA outflow elicited by electrical stimulation (300 microA, 1 ms, 20 Hz, 15 min)
of the dorsal raphe nucleus. Finally, GR 125487 (444 microg/kg, i.v.), whilst not
affecting basal firing of DA neurons within either the substantia nigra or the
ventral tegmental area, reduced HAL-stimulated (1–300 microg/kg, i.v.) impulse
flow of nigrostriatal DA neurons only. These results indicate that 5-HT4
receptors exert a facilitatory control on both striatal DA release and nigral DA
neuron impulse flow only when nigrostriatal DA transmission is under activated
conditions. Furthermore, they indicate that the striatum constitutes a major site
for the expression of the control exerted by 5-HT4 receptors on DA release. In
contrast, 5-HT4 receptors have no influence on mesoaccumbal DA activity in either
basal or activated conditions.


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