Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats
European Journal of Pharmacology. 2004-01-01; 484(2-3): 241-247
DOI: 10.1016/j.ejphar.2003.11.031
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O’Dell LE(1), Alomary AA, Vallée M, Koob GF, Fitzgerald RL, Purdy RH.
Author information:
(1)Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550
North Torrey Pines Road, La Jolla, CA 92037, USA.
Peripheral administration of alcohol has been demonstrated to cause significant
increases in neurosteroid levels in the brain and periphery. These findings have
led to several theories suggesting a role for neurosteroids in the actions of
alcohol. However, the anatomical sources of these steroids (e.g., brain or
periphery) are as yet unknown. This study utilized gas chromatography/mass
spectrometry (GC/MS) to assess the levels of several neuroactive steroids in
plasma and brain frontal cortex 30-360 min following acute administration of
alcohol (2 g/kg, i.p.). Concentrations of pregnenolone, allopregnanolone
(3alpha-hydroxy-5alpha-pregnan-20-one), and allotetrahydrodeoxycorticosterone
(3alpha,21-dihydroxy-5alpha-pregnan-20-one) were all measured. In order to
determine the contribution of peripheral endocrine organs to neurosteroid
responses, neuroactive steroid levels were measured in both intact and
adrenalectomized/gonadectomized male Wistar rats 30 min after acute
administration of alcohol. Intact animals exhibited a maximal increase of
pregnenolone in plasma and frontal cortex 30 min after acute administration of
alcohol. In addition, allopregnanolone levels increased, with a maximal effect
observed at 60 min in plasma. However, in the adrenalectomized/gonadectomized
groups treated with alcohol, no significant increases of pregnenolone,
allopregnanolone, or allotetrahydrodeoxycorticosterone were found after 30 min.
Thus, the alcohol-induced response was associated first with a relatively rapid
increase in the first and rate-limiting step in the conversion of cholesterol to
steroids, leading to increases in pregnenolone levels. This response was
followed by the further secretion of the anxiolytic neuroactive steroids
allopregnanolone and allotetrahydrodeoxycorticosterone, both of which appeared
to be of adrenal and gonadal origin.