Abstract：
:In this study, we investigated the modulatory effect of 5alpha-pregnan-3alpha-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(TBPS) in cerebral cortex, cerebellum, and hippocampus of control, ethanol-dependent, and ethanol-withdrawn rats. 5alpha-Pregnan-3alpha-ol-20-one potentiated the binding of [3H]flunitrazepam and [3H]muscimol in all the rat brain regions investigated in this study.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 (Emax) in the ethanol-dependent rat cerebellum as compared to control group (p<0. 025). Furthermore, 5alpha-pregnan-3alpha-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[35S]TBPS binding (-Emax) by 5alpha-pregnan-3alpha-ol-20-one in the hippocampus of ethanol-dependent as well as ethanol-withdrawn rats (p<0.025). These observations suggest that the neurosteroid binding site associated with the gamma-aminobutyric acidA (GABAA) 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.
journal_name
Brain Resjournal_title
Brain researchauthors
Mehta AK,Ticku MKdoi
10.1016/s0006-8993(98)00649-0subject
Has Abstractpub_date
1998-09-14 00:00:00pages
88-94issue
1-2eissn
0006-8993issn
1872-6240pii
S0006-8993(98)00649-0journal_volume
805pub_type
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