Monitoring Pathogen‐Induced Sickness in Mice and Rats

Daria Kolmogorova1, Emma Murray1, Nafissa Ismail2

1 School of Psychology, Faculty of Social Sciences, University of Ottawa, Ottawa, Ontario, 2 Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/cpmo.27
Online Posting Date:  June, 2017
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Sickness behavior monitoring, a technique for examining the development of sickness symptomatology following infection, is necessary in experiments studying neurochemical and physiological changes associated with pathogen‐induced immune activation. However, the results of sickness behavior monitoring are difficult to reconcile due to inconsistencies in protocol methods and rater bias. The protocol described herein offers a non‐invasive and unbiased approach to assess the progression of pathogen‐induced sickness behaviors. This simple, straightforward method uses a five‐point scale to assess animals for the presence of four sickness behaviors (i.e., ‘“0” = no sickness behaviors; “4” = four sickness behaviors) at various time points following exposure to a pathogen. This approach removes the ambiguity and bias inherent to other methods of sickness behavior monitoring that rely on subjective ratings of severity for individual symptoms. This protocol has been successfully applied to male and female rodents injected intraperitoneally with lipopolysaccharide and polyinosinic:polycytidylic acid, and has been effective in pubertal and adult populations. Protocols for changes in body temperature and weight are also provided as physiological markers of sickness. © 2017 by John Wiley & Sons, Inc.

Keywords: sickness; body weight; body temperature; rodent; pathogen; LPS; poly(I:C)

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Table of Contents

  • Introduction
  • Basic Protocol 1: Five‐Point Scale for Evaluating Pathogen‐Induced Sickness Behavior in Laboratory Mice and Rats
  • Support Protocol 1: Animal Housing and Care
  • Basic Protocol 2: Body Temperature Analyses Using Data‐Logger Implantation
  • Basic Protocol 3: Monitoring of Body Weight
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: Five‐Point Scale for Evaluating Pathogen‐Induced Sickness Behavior in Laboratory Mice and Rats

  • Rat or mouse subjects
  • LPS or Poly(I:C) solution (see recipes), prepared fresh
  • 0.9% (w/v) saline solution (sodium chloride), sterile
  • 27‐G × ½‐in needles
  • 1‐cc syringes
  • Sickness monitoring charts to score presence (score = 1) or absence (score = 0) of piloerection, ptosis, lethargy, and huddling

Support Protocol 1: Animal Housing and Care

  Additional Materials
  • Polycarbonate Lexan cages, for mice: 17 × 28 × 12–cm (width × length × height); for rats: 10 × 16 to 18 × 8.25–in
  • Teklad Corn Cob, 0.5‐in. diameter (Harlan Laboratories, Inc.)
  • Nestlet (Ancare Corp.)
  • Refuge hut made of cardboard (Ketchum Manufacturing, Inc., Brockville, Ontario)
  • PVC piping tube, 3.5‐ or 4.5‐in. diameter, 5‐in. long

Basic Protocol 2: Body Temperature Analyses Using Data‐Logger Implantation

  • 3% (v/v) children's Tylenol (acetaminophen)
  • Isoflurane
  • Endure 400 soap
  • Chlorhexidine gluconate solution
  • Bupivicaine
  • Carprofen
  • 1% alkaline liquid detergent
  • Subcue data‐loggers (; Calgary, AB, Canada)
  • Electric razor
  • Surgical tools
  • Sutures
  • Wound clips
  • Gaymar T/Pump classic heating pads
IMPORTANT: Read all operating instructions of the mini data‐loggers before proceeding. Mini data‐loggers should be tested and programmed prior to implantation, as instructed by the manufacturer.

Basic Protocol 3: Monitoring of Body Weight

  • Digital scale
  • Metal bowl (small enough to rest on the scale and large enough to hold a mouse or rat)
NOTE: The following steps should be completed following pathogen exposure. All weight measurements should be completed after sickness monitoring has been completed.
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Literature Cited

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