Chronic L-DOPA therapy alters central serotonergic function and L-DOPA-induced dopamine release in a region-dependent manner in a rat model of Parkinson's disease.
Neurobiol Dis
; 41(2): 585-90, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-21092759
ABSTRACT
The therapeutic benefit of L-DOPA is commonly attributed to restoration of dopamine (DA) extracellular levels in the striatum of Parkinsonian patients. However, the loss of efficacy of L-DOPA after chronic use is paradoxically associated with a similar or enhanced striatal DA response. Release of L-DOPA-derived DA depends on the widespread serotonergic (5-HT) innervation in the brain. Chronic exposure of 5-HT neurons to L-DOPA could lead to aberrant neurochemical responses beyond the striatum. Using multi-site intracerebral microdialysis in a rat model of Parkinson's disease, we showed that chronic L-DOPA treatment at a therapeutic dose (12 mg/kg/day for 10 days) homogeneously reduced basal 5-HT release and metabolism. These effects were paralleled by a decrease in tissue content of 5-HT and its metabolite. Chronic L-DOPA treatment severely altered the brain pattern of 5-HT and DA release responses to L-DOPA (3-12 mg/kg) with an overall loss of efficacy of L-DOPA to increase DA release. Our data demonstrate for the first time in vivo that the impairment of 5-HT neuronal function induced by chronic L-DOPA alters in a region-dependent manner L-DOPA-induced DA release. Changes in neurochemical pattern of L-DOPA in the brain may favour the occurrence of both motor and non-motor side effects.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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Encéfalo
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Dopamina
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Levodopa
/
Serotonina
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Francia