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Related Experiment Videos

Progesterone withdrawal I: pro-convulsant effects

M H Moran1, S S Smith

  • 1Department of Neurobiology and Anatomy, EPPI, 3200 Henry Ave., Allegheny Univ. of the Health Sciences, Philadelphia, PA 19129, USA.

Brain Research
|October 3, 1998
PubMed
Summary
This summary is machine-generated.

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Withdrawal from progesterone (P) can cause pro-convulsant effects, similar to benzodiazepines (BDZs). The neurosteroid 3alpha,5alpha-THP is identified as the active compound responsible for these seizure-exacerbating withdrawal properties.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Endocrinology

Background:

  • GABA-modulatory drugs like benzodiazepines (BDZs) are known to cause pro-convulsant withdrawal.
  • The role of neurosteroids in withdrawal syndromes is less understood.
  • Progesterone (P) is a precursor to neurosteroids, including 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP).

Purpose of the Study:

  • To test the hypothesis that withdrawal from the neurosteroid 3alpha,5alpha-THP, following sustained exposure to progesterone (P), produces pro-convulsant effects.
  • To investigate the role of 3alpha,5alpha-THP in P withdrawal-induced seizure activity.
  • To explore potential clinical relevance in women experiencing hormonal fluctuations.

Main Methods:

  • Rats were subjected to a chronic administration/withdrawal paradigm of progesterone (P).

Related Experiment Videos

  • Seizure activity was precipitated using picrotoxin or a benzodiazepine inverse agonist (beta-CC).
  • A 5alpha-reductase blocker (MK-906) was administered with P to identify the active metabolite.

    • Main Results:

    • Rats undergoing P withdrawal exhibited significantly greater seizure activity compared to controls.
    • Seizure scores in P-withdrawn rats were comparable to those seen in BDZ withdrawal.
    • Administration of a 5alpha-reductase blocker prevented the pro-convulsant effects of P withdrawal, implicating 3alpha,5alpha-THP.
    • Combined P and diazepam withdrawal showed synergistic pro-convulsant effects.

    Conclusions:

    • Progesterone (P) withdrawal induces pro-convulsant properties mediated by the neurosteroid 3alpha,5alpha-THP.
    • These findings suggest a potential mechanism for increased seizure incidence during declining P levels in women.
    • The study highlights the clinical relevance of neurosteroid withdrawal in conditions like epilepsy.