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.

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.