Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats

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...

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Veröffentlicht in:European journal of pharmacology 2004-01, Vol.484 (2), p.241-247
Hauptverfasser: O'Dell, Laura E., Alomary, Ahmed A., Vallée, Monique, Koob, George F., Fitzgerald, Robert L., Purdy, Robert H.
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container_issue 2
container_start_page 241
container_title European journal of pharmacology
container_volume 484
creator O'Dell, Laura E.
Alomary, Ahmed A.
Vallée, Monique
Koob, George F.
Fitzgerald, Robert L.
Purdy, Robert H.
description 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 (3α-hydroxy-5α-pregnan-20-one), and allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-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.
doi_str_mv 10.1016/j.ejphar.2003.11.031
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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 (3α-hydroxy-5α-pregnan-20-one), and allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-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. 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Drug treatments</subject><subject>Pregnanolone - blood</subject><subject>Pregnanolone - metabolism</subject><subject>Pregnenolone</subject><subject>Pregnenolone - blood</subject><subject>Pregnenolone - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Steroids - blood</subject><subject>Steroids - metabolism</subject><issn>0014-2999</issn><issn>1879-0712</issn><issn>1879-0712</issn><issn>0014-2999</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGL1DAUxoMo7uzqfyDSi8IeWvPatE0vwrKsrjDgRc_hNXl1MrTJmHQG1rN_uKkdnJunJB-_9_HyfYy9AV4Ah-bDvqD9YYehKDmvCoCCV_CMbUC2Xc5bKJ-zDecg8rLruit2HeOec153Zf2SXYFohWh4t2G_H-YdOj_m1pmjJpNZpwNhpJhumaNj8Khne6IszhS8NX_1eUdZwDnrA6YXOpMdRowTZhgowz6SmxcMTSCHI-nZT_ZXMl_IH96huUjJJr5iLwYcI70-nzfs-6eHb_eP-fbr5y_3d9tcCynnHEAa2UsEGvq-raqqEw0hUoN13XQ99kYYBD5QORhKCZi2b0QJvWmHqkPNqxt2u_rucFSHYCcMT8qjVY93W7VovKzKSsryBIl9v7KH4H8eKc5qslHTOKIjf4xKcoAuJZ9AsYI6-BgDDf-cgaulKbVXa1NqaUoBqNRUGnt79j_2E5nL0LmaBLw7Axg1jkNAp228cLVoZSWXT31cOUrJnSwFFbUll7q0IcWsjLf_3-QPqc212g</recordid><startdate>20040126</startdate><enddate>20040126</enddate><creator>O'Dell, Laura E.</creator><creator>Alomary, Ahmed A.</creator><creator>Vallée, Monique</creator><creator>Koob, George F.</creator><creator>Fitzgerald, Robert L.</creator><creator>Purdy, Robert H.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-3642-4257</orcidid></search><sort><creationdate>20040126</creationdate><title>Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats</title><author>O'Dell, Laura E. ; Alomary, Ahmed A. ; Vallée, Monique ; Koob, George F. ; Fitzgerald, Robert L. ; Purdy, Robert H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-118d8b8a1efbb7333946eaae6a5569babd4da10fe2fde712d7b6421bd7f39ac03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adrenalectomy</topic><topic>Allopregnanolone</topic><topic>Allotetrahydrodeoxycorticosterone</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cognitive science</topic><topic>Desoxycorticosterone - analogs &amp; derivatives</topic><topic>Desoxycorticosterone - blood</topic><topic>Desoxycorticosterone - metabolism</topic><topic>Endocrine response</topic><topic>Ethanol</topic><topic>Ethanol - administration &amp; dosage</topic><topic>Ethanol - blood</topic><topic>Ethanol - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuroscience</topic><topic>Orchiectomy</topic><topic>Pharmacology. Drug treatments</topic><topic>Pregnanolone - blood</topic><topic>Pregnanolone - metabolism</topic><topic>Pregnenolone</topic><topic>Pregnenolone - blood</topic><topic>Pregnenolone - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Steroids - blood</topic><topic>Steroids - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>O'Dell, Laura E.</creatorcontrib><creatorcontrib>Alomary, Ahmed A.</creatorcontrib><creatorcontrib>Vallée, Monique</creatorcontrib><creatorcontrib>Koob, George F.</creatorcontrib><creatorcontrib>Fitzgerald, Robert L.</creatorcontrib><creatorcontrib>Purdy, Robert H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>O'Dell, Laura E.</au><au>Alomary, Ahmed A.</au><au>Vallée, Monique</au><au>Koob, George F.</au><au>Fitzgerald, Robert L.</au><au>Purdy, Robert H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2004-01-26</date><risdate>2004</risdate><volume>484</volume><issue>2</issue><spage>241</spage><epage>247</epage><pages>241-247</pages><issn>0014-2999</issn><issn>1879-0712</issn><eissn>1879-0712</eissn><eissn>0014-2999</eissn><coden>EJPHAZ</coden><abstract>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 (3α-hydroxy-5α-pregnan-20-one), and allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-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.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>14744609</pmid><doi>10.1016/j.ejphar.2003.11.031</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-3642-4257</orcidid></addata></record>
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subjects Adrenalectomy
Allopregnanolone
Allotetrahydrodeoxycorticosterone
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Cognitive science
Desoxycorticosterone - analogs & derivatives
Desoxycorticosterone - blood
Desoxycorticosterone - metabolism
Endocrine response
Ethanol
Ethanol - administration & dosage
Ethanol - blood
Ethanol - pharmacology
Male
Medical sciences
Neuroscience
Orchiectomy
Pharmacology. Drug treatments
Pregnanolone - blood
Pregnanolone - metabolism
Pregnenolone
Pregnenolone - blood
Pregnenolone - metabolism
Rats
Rats, Wistar
Steroids - blood
Steroids - metabolism
title Ethanol-induced increases in neuroactive steroids in the rat brain and plasma are absent in adrenalectomized and gonadectomized rats
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