Chronic ethanol administration alters the modulatory effect of 5α- pregnan-3α-ol-20-one on the binding characteristics of various radioligands of GABA(A) receptors

Ashok K. Mehta, Maharaj K. Ticku

Resultado de la investigación: Articlerevisión exhaustiva

22 Citas (Scopus)

Resumen

In this study, we investigated the modulatory effect of 5α-pregnan- 3α-ol-20-one, a neurosteroid, on the binding characteristics of [3H]flunitrazepam (2 nM), [3H]muscimol (5 nM), and 4 nM [35S]t- butylbicyclophosphorothionate (TBPS) in cerebral cortex, cerebellum, and hippocampus of control, ethanol-dependent, and ethanol-withdrawn rats. 5α- Pregnan-3α-ol-20-one potentiated the binding of [3H]flunitrazepam and [3H]muscimol in all the rat brain regions investigated in this study. There was a significant increase in the maximal potentiation of [3H]flunitrazepam as well as [3H]muscimol binding (E(max)) in the ethanol-dependent rat cerebellum as compared to control group (p < 0.025). Furthermore, 5α- pregnan-3α-ol-20-one elicited a biphasic response, i.e., it potentiated the binding of [35S]TBPS at lower concentrations (≤ 100 nM) and inhibited the binding at higher concentrations (> 100 nM). There was a significant higher inhibition of [35S]TBPS binding (-E(max)) by 5α-pregnan-3α-ol-20-one in the hippocampus of ethanol-dependent as well as ethanolwithdrawn rats (p < 0.025). These observations suggest that the neurosteroid binding site associated with the γ-aminobutyric acid(A) (GABA(A)) receptors in cerebellum and hippocampus plays an important role during ethanol-dependence and ethanol-withdrawal, and some of the changes following ethanol dependence and its withdrawal may be mediated through the neurosteroid binding site.

Idioma originalEnglish (US)
Páginas (desde-hasta)88-94
Número de páginas7
PublicaciónBrain Research
Volumen805
N.º1-2
DOI
EstadoPublished - sept. 14 1998

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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