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Related Experiment Videos

Pregnancy reduces brain sigma receptor function.

R Bergeron1, C de Montigny, G Debonnel

  • 1Neuroscience Laboratory, Department of Psychiatry, Harvard Medical School, 940 Belmont Street, Brockton, MA, 0230 USA.

British Journal of Pharmacology
|September 14, 1999
PubMed
Summary
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Endogenous progesterone acts as a sigma receptor antagonist. This interaction influences sigma receptor function during pregnancy and postpartum, potentially impacting emotional states during these periods.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Sigma (sigma) receptors are newly cloned, with unidentified endogenous ligands.
  • Neuroactive steroids like progesterone exhibit high affinity for sigma receptors.
  • Sigma ligands can act as agonists (e.g., DTG, DHEA) or antagonists (e.g., haloperidol, progesterone) modulating NMDA receptor responses.

Purpose of the Study:

  • To investigate the role of endogenous progesterone in modulating sigma receptor activity.
  • To compare the effects of sigma agonists in female rats under different physiological conditions: control, late pregnancy, postpartum, and progesterone-treated ovariectomized states.

Main Methods:

  • Comparison of sigma agonist (DTG, (+)-pentazocine, DHEA) effects on NMDA receptor potentiation across four groups of female rats.
  • Assessment in control, day 18 pregnant, day 5 postpartum, and ovariectomized rats treated with high-dose progesterone for 3 weeks.

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Main Results:

  • Higher doses of sigma agonists were required to potentiate NMDA responses in pregnant and progesterone-treated rats compared to controls.
  • Postpartum rats and those after progesterone washout showed enhanced NMDA response potentiation by the sigma agonist DTG.
  • These findings indicate a shift in sigma receptor sensitivity during specific reproductive stages.

Conclusions:

  • Endogenous progesterone appears to function as an antagonist at sigma receptors.
  • Altered sigma receptor function during pregnancy and postpartum may be linked to emotional changes characteristic of these periods.
  • This research highlights the neurosteroid modulation of sigma receptors and its potential implications in reproductive neurobiology.