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Generation and On-Demand Initiation of Acute Ictal Activity in Rodent and Human Tissue
Published on: January 19, 2019
Effects of androsterone on convulsions in various seizure models in mice
Katarzyna Mróz1, Tomasz Mróz, Marian Wielosz
1Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland.
Abstract:
It is believed that a deficiency of androgens, including free testosterone, may promote the development of convulsions. The present study revealed differences in the action of androsterone (AND), a major excreted metabolite of testosterone and a neurosteroid, in three commonly used seizure models in mice. AND administered intraperitoneally exhibited dose-dependent protection against tonic-clonic convulsions caused by maximal electroshock (MES) with ED(50) (effective dose(50)) of 227 mg/kg. The compound also inhibited the convulsive action of pentylenetetrazole (PTZ), increasing its CD(50) (convulsive dose(50)) for clonic convulsions from 77.2 (PTZ + saline) to 93.9 (p < 0.05) for PTZ + AND 40 mg/kg and 113.9 mg/kg (p < 0.001) for PTZ + AND 60 mg/kg. In mice pretreated with 60 mg/kg AND, the CD(50) for PTZ-induced tonic convulsions increased from 102 to 127.6 mg/kg (p < 0.01). Surprisingly, doses of 50 and 100 mg/kg AND lowered the CD(50) for kainate (KA)-induced convulsions from 40.8 to 28.7 (p < 0.05) and 25.4 mg/kg (p < 0.001), respectively. In summary, for two of the mouse seizure models, our findings confirmed previous studies that demonstrated protective activity of AND. However, the potentiation of KA-induced convulsions by AND was somewhat unexpected and suggested that AND may also possess proconvulsant activity.
Insights
Androsterone (AND), a testosterone metabolite, shows protective effects against some seizures in mice. However, it unexpectedly increased kainate-induced convulsions, suggesting potential proconvulsant activity.
Area of Science:
- Neuroendocrinology
- Neuropharmacology
- Epileptology
Background:
- Androgen deficiency, including low free testosterone, is linked to seizure development.
- Androsterone (AND) is a major testosterone metabolite and a neurosteroid with potential central nervous system effects.
Purpose of the Study:
- To investigate the effects of androsterone (AND) on three distinct mouse seizure models.
- To determine if AND exhibits anticonvulsant or proconvulsant properties.
Main Methods:
- Mice were administered AND intraperitoneally.
- Seizure induction was achieved using maximal electroshock (MES), pentylenetetrazole (PTZ), and kainate (KA).
- Dose-dependent effects on convulsive thresholds (ED50, CD50) were evaluated.
Main Results:
- AND demonstrated dose-dependent protection against MES-induced tonic-clonic convulsions (ED50 = 227 mg/kg).
- AND increased the convulsive dose 50 (CD50) for PTZ-induced clonic and tonic convulsions.
- Unexpectedly, AND lowered the CD50 for KA-induced convulsions, indicating potentiation.
Conclusions:
- Androsterone exhibits anticonvulsant activity in MES and PTZ seizure models.
- The proconvulsant effect of AND on KA-induced seizures suggests a complex role in seizure modulation.
- Further research is needed to elucidate the dual action of AND in the central nervous system.

