Measurements And Metabolism Of Neurosteroids In The CNS

Alcohol Abuse And Alcoholism

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Abstract

The principal objective of this study is to determine the effect of ethanol on the metabolism of neurosteroids in the central nervous system. Neurosteroids such as 5a-pregnane-3a-ol-20-one (5a,3a-THP or Allopregnanolone) and 5a-pregnane-3a,21-diol-20- one(THDOC) have been shown to modulate the GABA/benzodiazepine binding sites and to exert anxiolytic and hypnotic effects. Modulation of these neurosteroids in the central nervous system by ethanol may be one of the underlying mechanisms for stress observed in human alcoholics especially during withdrawal. The GC/MS-NCI technique that we previousely established for the measurement of trace levels of neurosteroids in human cerebro spinal fluid (CSF) has been improved to include the analysis of progesterone and dihydroprogesterone, and extended to the analysis of human and rat plasma samples in this period. We were able to quantify pregnenolone, 5a,3a-, 5b,3a-, 5a,3b-THP, androsterone and dihydrotestosterone, dihydroprogesterone and progesterone in these samples. Using this technique, we continued to participate in the development of a pseudopregnancy model of catamenial epilepsy by NINDS investigators. Investigations on the effect of progesterone metabolism on post-partum depression are in progress in collaboration with NIMH. During this period, we extended our investigation into depressive illness by analyzing plasma and CSF samples of those patients with a history of depression and suicide attempts.