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1.
Exp Neurol ; 277: 35-45, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26687972

RESUMEN

The most effective treatment for Parkinson's disease (PD), l-DOPA, induces dyskinesia after prolonged use. We have previously shown that in 6-hydroxydopamine (6-OHDA) lesioned rats rendered dyskinetic by prolonged l-DOPA administration, lesion of the subthalamic nucleus (STN) reduces not only dyskinesias but also buspirone antidyskinetic effect. This study examined the effect of buspirone on STN neuron activity. Cell-attached recordings in parasagittal slices from naïve rats showed that whilst serotonin excited the majority of STN neurons, buspirone showed an inhibitory main effect but only in 27% of the studied cells which was prevented by the 5-HT1A receptor selective antagonist WAY-100635. Conversely, single-unit extracellular recordings were performed in vivo on STN neurons from four different groups, i.e., control, chronically treated with l-DOPA, 6-OHDA lesioned and lesioned treated with l-DOPA (dyskinetic) rats. In control animals, systemic-buspirone administration decreased the firing rate in a dose-dependent manner in every cell studied. This effect, prevented by WAY-100635, was absent in 6-OHDA lesioned rats and was not modified by prolonged l-DOPA administration. Altogether, buspirone in vivo reduces consistently the firing rate of the STN neurons through 5-HT1A receptors whereas ex vivo buspirone seems to affect only a small population of STN neurons. Furthermore, the lack of effect of buspirone in 6-OHDA lesioned rats, suggests the requirement of not only the activation of 5-HT1A receptors but also an intact nigrostriatal pathway for buspirone to inhibit the STN activity.


Asunto(s)
Buspirona/farmacología , Neuronas/efectos de los fármacos , Receptor de Serotonina 5-HT1A/metabolismo , Agonistas de Receptores de Serotonina/farmacología , Núcleo Subtalámico/citología , Potenciales de Acción/efectos de los fármacos , Adrenérgicos/toxicidad , Inhibidores de Captación Adrenérgica/farmacología , Animales , Desipramina/farmacología , Modelos Animales de Enfermedad , Dopaminérgicos/efectos adversos , Discinesia Inducida por Medicamentos/etiología , Discinesia Inducida por Medicamentos/prevención & control , Femenino , Levodopa/efectos adversos , Masculino , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Oxidopamina/toxicidad , Ratas , Ratas Sprague-Dawley
2.
J Anal Toxicol ; 17(3): 182-5, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8336493

RESUMEN

Headspace gas chromatography (HSGC) was used to measure the concentrations of acetone in samples of venous whole blood from drunk drivers (n = 500), hospital outpatients with type-I diabetes mellitus (n = 250), and healthy blood donors (n = 288). The standard deviation (SD) of blood-acetone determination by HSGC was 0.048 mg/L at a mean concentration of 2.34 mg/L (2.1%). The concentration of acetone in blood did not change significantly when the samples were stored at 4 degrees C for eight days. The ratio of the concentrations of acetone in plasma and whole blood was 1.23:1 (SD 0.229, n = 22). The frequency distributions of blood-acetone concentrations were markedly skewed to the right. The median concentration of acetone in blood from drunk drivers was 2.03 mg/L and the 2.5 and 97.5 percentiles were 0.80 and 12.8 mg/L, respectively. In patients with type-I diabetes mellitus, the median blood-acetone concentration was 1.90 mg/L and the 2.5 and 97.5 percentiles were 0.40 and 11.1 mg/L, respectively. In healthy blood donors, the median blood-acetone level was 1.26 mg/L and the 2.5 and 97.5 percentiles were 0.37 and 4.69 mg/L, respectively. The concentrations of acetone in blood did not differ appreciably among these three groups of subjects.


Asunto(s)
Acetona/sangre , Consumo de Bebidas Alcohólicas , Conducción de Automóvil , Donantes de Sangre , Diabetes Mellitus Tipo 1/sangre , Adulto , Cromatografía de Gases , Femenino , Humanos , Masculino , Suecia
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