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Neurobiol Aging ; 27(11): 1684-93, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16253392

RESUMEN

The steroid dehydroepiandrosterone (DHEA) is abundant in men and women and decreases rapidly during aging. Parkinson's disease (PD) is the second most common neurodegenerative disorder just behind Alzheimer. l-3,4-Dihydroxyphenylalanine (l-Dopa) therapy remains the most effective treatment but many patients develop motor complications. This study investigated the acute effect of DHEA alone and with l-Dopa in 12 females monkeys lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model PD. DHEA administration alone improved the mean parkinsonian score at 1, 5 and 15mg/kg in moderately and severely impaired MPTP monkeys and increased blood DHEA concentrations. DHEA with a low dose of l-Dopa increased the l-Dopa effect in moderately and severely impaired MPTP monkeys. DHEA lengthened duration of the effect of the low dose of l-Dopa by 15-45min. DHEA at 1, 5 and 15mg/kg combined with a high dose of l-Dopa did not increase dyskinesias. DHEA could act by reducing inhibitory GABAergic activity in the striatal output pathways. DHEA could also be metabolized into estradiol in the brain and increase acutely dopamine activity.


Asunto(s)
Antiparkinsonianos/farmacología , Deshidroepiandrosterona/farmacología , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/sangre , Antiparkinsonianos/farmacocinética , Deshidroepiandrosterona/administración & dosificación , Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/farmacocinética , Discinesia Inducida por Medicamentos/psicología , Femenino , Levodopa/administración & dosificación , Levodopa/farmacocinética , Levodopa/farmacología , Macaca fascicularis , Actividad Motora , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/psicología , Índice de Severidad de la Enfermedad
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