4 receptors selectively regulate the impulse-dependent exocytosis of dopamine in the rat striatum: In vivo studies with morphine, amphetamine and cocaine
Neuropharmacology. 2002-12-01; 43(7): 1099-1109
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Central serotonin4 receptors selectively regulate the impulse-dependent
exocytosis of dopamine in the rat striatum: in vivo studies with morphine,
amphetamine and cocaine.
Porras G(1), Di Matteo V, De Deurwaerdère P, Esposito E, Spampinato U.
(1)Laboratoire de Neuropsychobiologie des Désadaptations, UMR-CNRS 5541,
Université Victor Segalen Bordeaux 2, BP 31, 146, rue Léo Saignat, 33076,
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.