Central serotonin4 receptors selectively regulate the impulse-dependent exocytosis of dopamine in the rat striatum: in vivo studies with morphine, amphetamine and cocaine.
In vivo microdialysis and single-cell extracellular recordings were used to assess the involvement of serotonin(4) (5-HT(4)) receptors in the effects induced by morphine, amphetamine and cocaine on nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity. The increase in striatal DA release induced by morphine (2.5 mg/kg, s.c.) was significantly reduced by the selective 5-HT(4) antagonists GR 125487 (0.1 and 1 mg/kg, i.p.) or SB 204070 (1 mg/kg, i.p.), and potentiated by the 5-HT(4) agonist prucalopride (5 mg/kg, i.p.). Neither of these compounds affected morphine-stimulated DA release in the nucleus accumbens. In both regions, amphetamine (2 mg/kg, i.p.) and cocaine (15 mg/kg, i.p.) induced DA release was affected neither by GR 125487 nor by prucalopride. None of the 5-HT agents used modified basal DA release in either brain region. Finally, GR 125487 (445 microg/kg, i.v.), whilst not affecting basal firing of DA neurons within either the substantia nigra pars compacta nor the ventral tegmental area, significantly reduced morphine (0.1-10 mg/kg, i.v.) stimulated firing of nigrostriatal DA neurons only. These results confirm that 5-HT(4) receptors exert a state-dependent facilitatory control restricted to the nigrostriatal DA pathway, and indicate that 5-HT(4) receptors selectively modulate DA exocytosis associated with increased DA neuron firing rate.
Porras
Grégory
G
Laboratoire de Neuropsychobiologie des Désadaptations, UMR-CNRS 5541, Université Victor Segalen Bordeaux 2, BP 31, 146, rue Léo Saignat, 33076, Bordeaux, France.
Di Matteo
Vincenzo
V
De Deurwaerdère
Philippe
P
Esposito
Ennio
E
Spampinato
Umberto
U
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; D009020:Morphine; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine