Metabolism Of Neurosteroids In The Central Nervous Syste

Alcohol Abuse And Alcoholism

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Abstract

The principal objective of this study is to determine the effect of ethanol on the[unreadable] metabolism of neurosteroids in the central nervous system. Neurosteroids such as[unreadable] 5a-pregnane-3a-ol-20-one (5a,3a-THP or Allopregnanolone) and[unreadable] 5a-pregnane-3a,21-diol-20- one(THDOC) have been shown to modulate the[unreadable] GABA/benzodiazepine binding sites and to exert anxiolytic and hypnotic effects.[unreadable] Modulation of these neurosteroids in the central nervous system by ethanol may be one[unreadable] of the underlying mechanisms for stress observed in human alcoholics especially during[unreadable] withdrawal. The GC/MS-NCI technique that we previousely established for the[unreadable] measurement of trace levels of neurosteroids in human cerebro spinal fluid (CSF) has[unreadable] been extended to the analysis of rat tissue samples in this period. We were able[unreadable] to establish a procedure to quantify pregnenolone, 5a,3a-, 5b,3a-, 5a,3b-THP, and[unreadable] dihydrotestosterone, dihydroprogesterone and progesterone in these samples. During this period, further analysis of previously obtained data has been performed and two collaborative papers were published, but no staff time was devoted to obtain new data although the project has not been inactivated completely.