Interaction of pregnanolone and pregnenolone sulfate with ethanol and pentobarbital

• Published in: Pharmacology, biochemistry and behavior Vol. 42; no. 4; pp. 605 - 611
• Main Authors: Melchior, Christine L., Allen, Pamela M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1992; Elsevier Science
• Subjects: Alcohol; Animals; Benzodiazepine; Biological and medical sciences; Body Temperature - drug effects; Dose-Response Relationship, Drug; Drug Interactions; Ethanol - pharmacology; Hormones. Endocrine system; Hypothermia; Male; Medical sciences; Mice; Mice, Inbred C57BL; Motor activity; Motor Activity - drug effects; Neurosteroid; Pentobarbital; Pentobarbital - pharmacology; Pentylenetetrazole; Pharmacology. Drug treatments; Pregnanolone - pharmacology; Pregnenolone; Pregnenolone - pharmacology; Pregnenolone sulfate; Seizures - prevention & control; Sleep - drug effects; Sleep time; Time Factors; Pregnenolone sulfate; Sleep time; Pentobarbital; Motor activity; Benzodiazepine; Alcohol; Neurosteroid; Pentylenetetrazole; Pregnenolone; Hypothermia; Agonist; Drug alcohol interaction; Intraperitoneal administration; Ethanol; Steroid hormone; Rodentia; Pregnanolone; Progestagen; Gabaergic receptor; Vertebrata; Mammalia; Mouse; Animal; Drug interaction; Antagonist; Behavior; Barbituric
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/0091-3057(92)90005-Z

3-α-Hydroxy-5-β-pregnan-20-one [pregnanolone (Pa)] and 3-β-hydroxy-5-pregnen-20-one 3-sulfate [pregnenolone sulfate (PS)] are steroids that have been shown in biochemical studies to be active at the GABA-benzodiazepine-chloride receptor complex, Pa as a “barbiturate-like” agonist and PS as a “picrotoxin-like” antagonist. Since other compounds that are active at this site interact with the effects of pentobarbital and ethanol, the behavioral effects of these steroids alone and in combination with pentobarbital and ethanol were tested. Pa blocks the convulsions caused by pentylenetetrazole (PTZ) and increases motor activity when given alone in low doses. In combination with either pentobarbital or ethanol, it enhances the depression in motor activity, hypothermia, and hypnosis. In contrast, PS has no effect on PTZ convulsions and depresses motor activity by itself. With pentobarbital, PS enhances the depression in motor activity but has no effect on hypothermia or hypnosis. With ethanol, PS enhances the hypothermia but does not affect motor activity or hypnosis. Therefore, Pa and PS show different but no opposite effects in interacting with compounds active at the GABA-benzodiazepine-chloride receptor complex.