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 extended to the analysis of rat tissue samples in this period. We were able to establish a procedure to quantify pregnenolone, 5a,3a-, 5b,3a-, 5a,3b-THP, and dihydrotestosterone, dihydroprogesterone and progesterone in these samples. During this period, the limited staff time was devoted to finishing data analysis of the previous studies regarding the effect of progesterone metabolism on premenstral and post-partum depression in collaboration with NIMH.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000089-10
Application #
6982881
Study Section
(LMBB)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Bloch, Miki; Rubinow, David R; Berlin, Kate et al. (2006) Monoamines and neurosteroids in sexual function during induced hypogonadism in healthy men. Arch Gen Psychiatry 63:450-6
Nieminen, L R G; Makino, K K; Mehta, N et al. (2006) Relationship between omega-3 fatty acids and plasma neuroactive steroids in alcoholism, depression and controls. Prostaglandins Leukot Essent Fatty Acids 75:309-14