Modification of behavioral effects of drugs in mice by neuroactive steroids
| Autor: | Jeffrey M. Witkin, Durk Dijkstra, M Beekman, Maciej Gasior, Jesse T. Ungard, Richard B. Carter |
|---|---|
| Přispěvatelé: | Groningen Research Institute of Pharmacy |
| Rok vydání: | 2000 |
| Předmět: |
Male
Ganaxolone Convulsants Pregnanolone Pharmacology neuroactive steroids Synaptic Transmission Mice chemistry.chemical_compound Cocaine Dopamine Uptake Inhibitors dizocilpine ANXIETY yohimbine NEUROSTEROIDS gamma-Aminobutyric Acid Behavior Animal GABAA receptor PENTYLENETETRAZOL ANTICONVULSANT Pregnenolone DIAZEPAM Anticonvulsants Steroids bicuculline medicine.drug medicine.medical_specialty Neuroactive steroid Motor Activity Internal medicine medicine Animals Pentylenetetrazol methamphetamine Phencyclidine GAMMA-AMINOBUTYRIC-ACID Psychotropic Drugs RECEPTOR Dose-Response Relationship Drug business.industry Allopregnanolone picrotoxin Endocrinology Anxiogenic chemistry GANAXOLONE Pentylenetetrazole Central Nervous System Stimulants locomotor activity business |
| Zdroj: | Psychopharmacology, 148(4), 336-343. SPRINGER |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s002130050060 |
| Popis: | Rationale: Neuroactive steroids represent a novel class of potential therapeutic agents (epilepsy, anxiety, migraine, drug dependence) thought to act through positive allosteric modulation of the GABA(A) receptor A synthetically derived neuroactive steroid, ganaxolone (3 alpha-hydroxy-3 beta-methyl-5 alpha-pregnan-20-one), is in phase-II clinical trials for epilepsy. Unlike traditional anticonvulsants such as diazepam and phenobarbital, ganaxolone shows equipotent suppression of both the seizure activity and the behavioral effects of pentylenetetrazol (PTZ) administration. Objectives: The present study explored possible reversal by ganaxolone and related neuroactive steroids of some behavioral effects of additional pharmacological challenges. Methods: Direct behavioral observation and photocell-counted locomotor activity of male, Swiss-Webster mice were made with various compounds alone and in conjunction with ganaxolone. Results: Ganaxolone both prevented and reversed PTZ-induced locomotor depression in mice. Further, ganaxolone reversed the locomotor depression induced by other convulsant/anxiogenic stimuli: bituculline, picrotoxin and, to a lesser extent, yohimbine. Ganaxolone failed to reverse the locomotor stimulation induced by cocaine, methamphetamine, dizocilpine, and phencyclidine. In addition to ganaxolone, the endogenous neuroactive steroids allopregnanolone and pregnanolone and the synthetic neuroactive steroid Co 2-1068 also reversed observed behaviors and locomotor depression induced by PTZ. Conclusions: The present findings support the unique pharmacological effects of neuroactive steroids as a novel class of positive allosteric modulators of GABA. |
| Databáze: | OpenAIRE |
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