Cannabinoid‐Induced Tetrad in Mice

Mathilde Metna‐Laurent1, Miguel Mondésir2, Agnès Grel2, Monique Vallée2, Pier‐Vincenzo Piazza2

1 Aelis Farma, Neurocentre Magendie, Bordeaux, 2 University of Bordeaux, Bordeaux
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.59
DOI:  10.1002/cpns.31
Online Posting Date:  July, 2017
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Cannabinoid‐induced tetrad is a preclinical model commonly used to evaluate if a pharmacological compound is an agonist of the central type‐1 cannabinoid (CB1) receptor in rodents. The tetrad is characterized by hypolocomotion, hypothermia, catalepsy, and analgesia, four phenotypes that are induced by acute administration of CB1 agonists exemplified by the prototypic cannabinoid delta‐9‐tetrahydrocannabinol (THC). This unit describes a standard protocol in mice to induce tetrad phenotypes with THC as reference cannabinoid. We provide typical results obtained with this procedure showing a dose effect of THC in different mouse strains. The effect of the CB1 antagonist rimonabant is also shown. This tetrad protocol is well adapted to reveal new compounds acting on CB1 receptors in vivo. © 2017 by John Wiley & Sons, Inc.

Keywords: cannabinoid; tetrad; CB1 receptors; mice

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Table of Contents

  • Introduction
  • Basic Protocol 1: THC‐Induced Tetrad in Mice
  • Support Protocol 1: Blockade of THC‐Induced Tetrad by the CB1 Receptor Antagonist Rimonabant
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: THC‐Induced Tetrad in Mice

  • 2 to 3 month‐old naïve male C57Bl/6J mice
  • 20% ethanol
  • Delta‐9‐tetrahydrocannabinol (THC) solution (see recipe)
  • Vehicle control solution for THC
  • Scale, to weight mice
  • Flexible rectal probe (e.g., Physitemp RET‐3) and monitoring thermometer (e.g., Physitemp TH‐5)
  • 1‐ml syringes
  • 25‐G needles, 16 × 0.5 mm
  • Behavioral testing room containing:
    • Open field area (made in house)
    • Video camera
    • Hot plate
    • Catalepsy cages (made in house)
    • Chronometer
NOTE: All protocols using live animals must first be reviewed and approved by an Institutional Animal Care and Use Committee (IACUC) or must conform to governmental regulations regarding the care and use of laboratory animals.NOTE: The use of cannabinoid agents for preclinical research requires specific authorization from local regulatory authorities. In general, the investigator needs authorization before ordering and using cannabinoids that are listed as psychotropic drugs for animal research. The application for authorization describes the purpose of the animal project and the exact amount of drugs required for the development of the project. The use of cannabinoid drugs is tracked and checked by the authorities.
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Literature Cited

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