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Effects of chronic ethanol consumption and withdrawal on the neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one in male and female rats. 1998

G C Janis, and L L Devaud, and H Mitsuyama, and A L Morrow
Bowles Center for Alcohol Studies, Curriculum in Toxicology, University of North Carolina School of Medicine, Chapel Hill 27599-7178, USA.

Prolonged alcohol (ethanol) consumption leads to the development of alcohol tolerance and cross-tolerance to some benzodiazepines and barbiturates. In contrast, rats undergoing alcohol withdrawal are sensitized to the anticonvulsant effects of the endogenous GABA(A) receptor modulator, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP). Alterations in endogenous, cerebral cortical levels of 3alpha,5alpha-THP during alcohol withdrawal could contribute to the observed sensitization to 3alpha,5alpha-THP. Therefore, this study investigated plasma and brain levels of 3alpha,5alpha-THP, progesterone, and corticosterone during alcohol dependence and withdrawal in the rat. Plasma corticosterone, progesterone (a precursor of 3alpha,5alpha-THP) and 3alpha,5alpha-THP levels were unchanged in alcohol-dependent animals. Cerebral cortical levels of 3alpha,5alpha-THP decreased in dependent male animals, but not in dependent female rats. During alcohol withdrawal, plasma corticosterone and progesterone levels increased in male, but not female rats. However, neither plasma nor cerebral cortical 3alpha,5alpha-THP levels were altered from control levels in male or female rats during alcohol withdrawal. Plasma and brain levels of 3alpha,5alpha-THP were markedly higher in female compared with male rats. Cerebral cortical levels of 3alpha,5alpha-THP during the diestrus phase of the estrus cycle were approximately 4 to 6 ng/g, a concentration that may approach physiological relevance. These findings suggest that sensitization to 3alpha,5alpha-THP during alcohol withdrawal is not mediated by elevations in brain levels of endogenous 3alpha,5alpha-THP in male or female rats. However, elevations in circulating corticosterone and progesterone levels during ethanol withdrawal in male rats may underlie gender differences in allopregnanolone sensitivity during ethanol withdrawal.

UI MeSH Term Description Entries
D008297 Male Males
D011280 Pregnanolone A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties. Eltanolone,3 alpha, 5 beta-Tetrahydroprogesterone,3 alpha-Hydroxy-5 alpha-pregnan-20-one,3 alpha-Hydroxy-5 beta-pregnan-20-one,3-Hydroxypregnan-20-one,3beta-Hydroxy-5alpha-pregnan-20-one,Allopregnan-3 beta-ol-20-one,Allopregnanolone,Epipregnanolone,Pregnan-3alpha-ol-20-one,Pregnanolone, (3alpha)-isomer,Pregnanolone, (3alpha, 5beta, 17-alpha)-isomer,Pregnanolone, (3alpha,5alpha)-isomer,Pregnanolone, (3alpha,5beta)-isomer,Pregnanolone, (3beta)-isomer,Pregnanolone, (3beta, 5alpha)-isomer,Pregnanolone, (3beta, 5alpha, 17alpha)-isomer,Pregnanolone, (3beta, 5alpha, 8alpha, 17beta)-isomer,Pregnanolone, (3beta, 5beta)-isomer,Pregnanolone, (3beta, 5beta, 17alpha)-isomer,Pregnanolone, (3beta, 5beta,14beta)-isomer,Pregnanolone, (5alpha)-isomer,Sepranolone,3 Hydroxypregnan 20 one,3 alpha Hydroxy 5 alpha pregnan 20 one,3 alpha Hydroxy 5 beta pregnan 20 one,3 alpha, 5 beta Tetrahydroprogesterone,3beta Hydroxy 5alpha pregnan 20 one,Allopregnan 3 beta ol 20 one,Pregnan 3alpha ol 20 one,alpha-Hydroxy-5 alpha-pregnan-20-one, 3,alpha-Hydroxy-5 beta-pregnan-20-one, 3,alpha-pregnan-20-one, 3 alpha-Hydroxy-5,beta-ol-20-one, Allopregnan-3,beta-pregnan-20-one, 3 alpha-Hydroxy-5
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004971 Estrus The period in the ESTROUS CYCLE associated with maximum sexual receptivity and fertility in non-primate female mammals.
D005260 Female Females
D000430 Alcohol Withdrawal Delirium An acute organic mental disorder induced by cessation or reduction in chronic alcohol consumption. Clinical characteristics include CONFUSION; DELUSIONS; vivid HALLUCINATIONS; TREMOR; agitation; insomnia; and signs of autonomic hyperactivity (e.g., elevated blood pressure and heart rate, dilated pupils, and diaphoresis). This condition may occasionally be fatal. It was formerly called delirium tremens. (From Adams et al., Principles of Neurology, 6th ed, p1175) Alcohol Withdrawal Hallucinosis,Autonomic Hyperactivity, Alcohol Withdrawal Associated,Delirium Tremens,Alcohol Withdrawal Associated Autonomic Hyperactivity,Alcohol Withdrawal-Induced Delirium Tremens,Delirium Tremens, Alcohol Withdrawal Induced,Alcohol Withdrawal Induced Delirium Tremens,Delirium, Alcohol Withdrawal,Hallucinosis, Alcohol Withdrawal
D000437 Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4) Alcohol Abuse,Alcoholic Intoxication, Chronic,Ethanol Abuse,Alcohol Addiction,Alcohol Dependence,Alcohol Use Disorder,Abuse, Alcohol,Abuse, Ethanol,Addiction, Alcohol,Alcohol Use Disorders,Chronic Alcoholic Intoxication,Dependence, Alcohol,Intoxication, Chronic Alcoholic,Use Disorders, Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012737 Sex Factors Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances. Factor, Sex,Factors, Sex,Sex Factor
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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