English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/89185
Título

Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action

AutorMocci, Giuseppe ; Jiménez-Sánchez, Laura ; Adell, Albert ; Cortés, Roser ; Artigas, Francesc
Palabras claveAtypical antipsychotics
Dopamine
Mesolimbic pathway
Pyramidal neurons
Schizophrenia
Serotonin receptors
Fecha de publicaciónnov-2013
EditorElsevier
CitaciónNeuropharmacology 79: 49-58 (2013)
ResumenThe prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially target cortical serotonin (5-HT) receptors. The brain networks involved in the therapeutic action of atypical drugs are not fully understood. Previous work indicated that medial PFC (mPFC) pyramidal neurons projecting to ventral tegmental area express 5-HT2A receptors suggesting that atypical antipsychotic drugs modulate dopaminergic activity distally, via 5-HT2A receptor (5-HT2A-R) blockade in PFC. Since the mPFC also projects heavily to NAc, we examined whether NAc-projecting pyramidal neurons also express 5-HT2A-R. Using a combination of retrograde tracing experiments and in situ hybridization we report that a substantial proportion of mPFC-NAc pyramidal neurons in rat brain express 5-HT2A-R mRNA in a layer- and area-specific manner (up to 68% in layer V of contralateral cingulate). The functional relevance of 5-HT2A-R to modulate mPFC-NAc projections was examined in dual-probe microdialysis experiments. The application of the preferential 5-HT2A-R agonist DOI into mPFC enhanced glutamate release locally (+66 ± 18%) and in NAc (+74 ± 12%) indicating that cortical 5-HT2A-R activation augments glutamatergic transmission in NAc. Since NAc integrates glutamatergic and dopaminergic inputs, blockade of 5-HT2A-R by atypical drugs may reduce cortical excitatory inputs onto GABAergic neurons of NAc, adding to dopamine D2 receptor blockade. Together with previous observations, the present results suggest that atypical antipsychotic drugs may control the activity of the mesolimbic pathway at cell body and terminal level.
Versión del editorhttp://dx.doi.org/10.1016/j.neuropharm.2013.10.021
URIhttp://hdl.handle.net/10261/89185
DOI10.1016/j.neuropharm.2013.10.021
ISSN0028-3908
E-ISSN1873-7064
Aparece en las colecciones: (IIBB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Expression of 5-HT2A.pdf653,4 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.