An Animal Model of Premenstrual Dysphoric Disorder Sensitive to Antidepressants

Tomasz Schneider1, Piotr Popik1

1 Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.31
DOI:  10.1002/0471142301.ns0931s46
Online Posting Date:  January, 2009
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Abstract

Premenstrual dysphoric disorder (PMDD) is characterized by the recurrence of a cluster of physical and negative mood symptoms, especially irritability, appearing when estrogen and progesterone levels decrease during the late luteal phase of the menstrual cycle. This unit describes a new animal model of PMDD that shows differentiation between female rats expressing and not expressing ovarian cycle–dependent irritability measured by the behavior of burying harmless objects. Burying behavior is enhanced in a subgroup of female rats at metestrus and decreased at the proestrus phase of the estrous cycle. Increased marble burying at metestrus does not habituate and can be reversed by acute treatment with several antidepressants, which mimic the pharmacology of PMDD in humans. This model may be used to study the neuroendocrine mechanisms triggering premenstrual irritability, and the mode of action of antidepressants used for the treatment of PMDD. Curr. Protoc. Neurosci. 46:9.31.1‐9.31.10. © 2009 by John Wiley & Sons, Inc.

Keywords: animal model; irritability; marble‐burying test; premenstrual dysphoric disorder; antidepressants

     
 
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Table of Contents

  • Introduction
  • Basic Protocol 1: Measuring Estrous Cycle–Dependent Irritability in Rats
  • Basic Protocol 2: Determination of Estrous Cycle Phases in Rat
  • Support Protocol 1: Measuring Activity in Female Rats
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Measuring Estrous Cycle–Dependent Irritability in Rats

  Materials
  • Mature female Wistar rats (at least 3 months old)
  • Standard laboratory rodent chow
  • Test agents:
    • Fluoxetine HCl (Sigma‐Aldrich): 5 mg/kg, administered i.p. in distilled water in a volume of 2 ml/kg, 4 hr before testing
    • Progesterone (4‐Pregnene‐3,20‐dione, Sigma cat. no. P‐0130): 1 mg/kg, administered s.c. in corn oil in a volume of 0.4 ml/rat, 4 hr before testing
  • Housing room with regulated light/dark cycle, maintained at 21°C
  • Non‐toxic permanent black marker
  • Single rat cages (∼47‐cm length × 27‐cm width × 15‐cm height)
  • Sawdust bedding
  • White noise generator to mask ambient noise (e.g., AM radio receiver set at low/middle volume: ∼60 dB)
  • Glass marbles (∼2 cm in diameter, available from a local craft store)

Basic Protocol 2: Determination of Estrous Cycle Phases in Rat

  Materials
  • Ear sticks (cotton swab, Q‐tip)
  • Glass slides
  • Light microscope

Support Protocol 1: Measuring Activity in Female Rats

  Materials
  • Mature female Wistar rats (at least 3 months old)
  • Automated or manually operated open field (unit 8.1)
  • Compounds used in the marble burying behavior test (see protocol 1)
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Figures

Videos

Literature Cited

Literature Cited
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