Repeated cocaine administration decreases 5-HT(2A) receptor-mediated serotonergic enhancement of synaptic activity in rat medial prefrontal cortex.
Neuropsychopharmacology
; 34(8): 1979-92, 2009 Jul.
Article
en En
| MEDLINE
| ID: mdl-19212317
ABSTRACT
Neural adaptations in the medial prefrontal cortex (mPFC) are thought to be crucial in the development and maintenance of addictive behaviors. The mPFC receives a dense serotonergic (5-hydroxytryptamine, 5-HT) innervation from raphe nuclei and 5-HT exerts complex actions on mPFC pyramidal neurons. The present study, using a rat model of behavioral sensitization to cocaine, was designed to determine whether repeated cocaine exposure in vivo is capable of altering 5-HT-induced regulation of glutamatergic transmission in the mPFC. In layer V pyramidal neurons of the mPFC, application of 5-HT, through activation of 5-HT(2A) receptors, induced a massive enhancement of spontaneous excitatory postsynaptic currents (sEPSCs). Repeated cocaine administration for 5 days resulted in an attenuation in the ability of 5-HT to enhance sEPSCs. This effect was prevented when cocaine was co-administered with the selective 5-HT(2A) receptor antagonist ketanserin and was mimicked by repeated 5-HT(2A) receptor agonist (-)4-iodo-2,5-dimethoxyphenylisopropylamine administration. Repeated cocaine administration is not associated with any changes in the levels of 5-HT(2A) receptors or regulator of GTP-binding protein signaling 4. These results suggest that cocaine-induced inhibition of 5-HT(2A) receptor-mediated enhancement of glutamatergic transmission in the mPFC may be caused, at least in part, by the impairment of coupling of 5-HT(2A) receptors with GTP-binding proteins during cocaine withdrawal. These alterations in 5-HT(2A) receptor responsiveness in the mPFC may be relevant to the development of behavioral sensitization and withdrawal effects following repeated cocaine administration.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Abstinencia a Sustancias
/
Serotonina
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Corteza Prefrontal
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Cocaína
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Trastornos Relacionados con Cocaína
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Antagonistas del Receptor de Serotonina 5-HT2
Límite:
Animals
Idioma:
En
Revista:
Neuropsychopharmacology
Asunto de la revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Taiwán