RESUMEN
The potential influence of the neurosteroid pregnenolone sulfate (PrS) on barbiturate-induced hypnosis was tested in rats. PrS, when injected intracerebroventricularly or intraperitoneally, significantly shortened the sleep-time produced by pentobarbital. The results suggest an important physiological and pharmacological role for PrS in the regulation of CNS excitability.
Asunto(s)
Hipnosis Anestésica , Pentobarbital/farmacología , Pregnenolona/farmacología , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Masculino , Pregnenolona/administración & dosificación , Ratas , Ratas Endogámicas F344 , Ratas EndogámicasRESUMEN
The effect of ethanol on the binding of gamma-aminobutyric acid (GABA) agonist, [3H]muscimol, to crude synaptosomal membranes prepared from various rat brain regions was investigated, in vitro, at 37 degrees C. Ethanol altered specific muscimol binding in a biphasic manner--reducing it at concentrations less than 10 mM and subsequently increasing specific binding at concentrations greater than 10 mM. The former effect was due to a decrease of the receptor affinity for an agonist, and the latter, due to an increase of the receptor density. Ethanol interfered also with the effects of "GABAergic" modulatory steroids on muscimol binding. This suggests that steroid-ethanol interactions, occurring at the level of the plasma membrane, may be involved in the molecular mechanism of action of ethanol on the GABAA receptor.
Asunto(s)
Encéfalo/metabolismo , Etanol/farmacología , Receptores de GABA-A/metabolismo , Esteroides/farmacología , Animales , Unión Competitiva , Cerebelo/metabolismo , Corteza Cerebral/metabolismo , Ditiotreitol/farmacología , Interacciones Farmacológicas , Hipocampo/metabolismo , Hipotálamo/metabolismo , Técnicas In Vitro , Muscimol/farmacología , Ratas , Receptores de GABA-A/efectos de los fármacosRESUMEN
The A-ring reduced metabolite of deoxycorticosterone, 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) was recently shown to act at the gamma-aminobutyric acid receptor-chloride ion channel complex in rat brain. The behavioral profile of THDOC was investigated using two animal models of anxiety, the two-chambered mouse exploration test and the lick suppression conflict test. THDOC showed anxiolytic activity in both animal models, with an anxiolytic dose range, 5-15 mg/kg i.p., separable from the sedative dose range, above 20-30 mg/kg i.p.