Thromboxane receptor activation enhances striatal dopamine release, leading to suppression of GABAergic transmission and enhanced sugar intake.
Eur J Neurosci
; 34(4): 594-604, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21749493
ABSTRACT
The extracellular dopamine level is regulated not only by synaptic inputs to dopamine neurons but also by local mechanisms surrounding dopaminergic terminals. However, much remains to be investigated for the latter mechanism. Thromboxane A(2) is one of the cyclooxygenase products derived from arachidonic acid, and acts on its cognate G protein-coupled receptor [thromboxane receptor (TP)]. We show here that TP in the striatum locally facilitates dopamine overflow. Intrastriatal injection of a TP agonist increased extracellular dopamine levels in the striatum as measured by in vivo microdialysis. TP stimulation also augmented electrically evoked dopamine overflow from striatal slices. Conversely, TP deficiency reduced dopamine overflow evoked by N-methyl-d-aspartic acid (NMDA) and acetylcholine in striatal slices. TP immunostaining showed that TP is enriched in vascular endothelial cells. Pharmacological blockade of nitric oxide (NO) synthesis and genetic deletion of endothelial NO synthase (eNOS) suppressed NMDA/acetylcholine-induced dopamine overflow. This involvement of NO was abolished in TP-deficient slices, suggesting a role for eNOS-derived NO synthesis in TP-mediated dopamine overflow. As a functional consequence of TP-mediated dopamine increase, a TP agonist suppressed GABAergic inhibitory postsynaptic currents in medium spiny neurons through a D2-like receptor-dependent mechanism. Finally, TP is involved in sucrose intake, a dopamine-dependent motivational behavior. These data suggest that TP stimulation in the striatum locally facilitates dopamine overflow evoked by synaptic inputs via NO synthesis in endothelial cells.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dopamina
/
Receptores de Tromboxanos
/
Transmissão Sináptica
/
Corpo Estriado
/
Comportamento Alimentar
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Japão