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The neurosteroid, 3 alpha-hydroxy-5 alpha-pregnan-20-one, protects against bicuculline-induced seizures during ethanol withdrawal in rats. 1995

L L Devaud, and R H Purdy, and A L Morrow
Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7175, USA.

Prolonged alcohol consumption leads to the development of tolerance to and dependence on ethanol, resulting in a decreased response to the sedative/hypnotic effects of ethanol, and by negative symptomatology following abrupt termination of use. One symptom associated with ethanol withdrawal in humans, as well as laboratory animals, is enhanced susceptibility to seizures. This study investigated the effects of the neurosteroid, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-5 alpha-THP), on alterations in seizure sensitivity associated with ethanol withdrawal. 3 alpha-5 alpha-THP is a potent anxiolytic and anticonvulsant agent that acts via selective interactions with GABAA receptors. Extensive evidence suggests that some aspects of ethanol dependence and withdrawal are mediated by alterations in GABAA receptor function. Withdrawal from chronic ethanol exposure elicited dramatic increases in seizure susceptibility in male and female rats. Administration of 3 alpha-5 alpha-THP just before seizure threshold determinations blocked the increased seizure susceptibility induced by ethanol withdrawal. Ethanol-withdrawn animals were protected by 3 alpha-5 alpha-THP at a dose that had no effect on control animal seizure thresholds. Moreover, male and female rats displayed differential responses to the seizure-threshold lowering effects of ethanol withdrawal, as well as the protection by 3 alpha-5 alpha-THP pretreatment. These findings suggest that there are gender differences associated both with ethanol withdrawal as well as the protection by 3 alpha-5 alpha-THP in ethanol-dependent rats.

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
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
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
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
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic

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