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
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

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

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

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
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: THC‐Induced Tetrad in Mice

  Materials
  • 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.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
  Ahn, K. H., Mahmoud, M. M., Shim, J.‐Y., & Kendall, D. A. (2013). Distinct roles of β‐arrestin 1 and β‐arrestin 2 in ORG27569‐induced biased signaling and internalization of the cannabinoid receptor 1 (CB1). Journal of Biological Chemistry, 288, 9790–9800. doi: 10.1074/jbc.M112.438804.
  Bénard, G., Massa, F., Puente, N., Lourenço, J., Bellocchio, L., Soria‐Gómez, E., … Marsicano, G. (2012). Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nature Neuroscience, 15, 558–564. doi: 10.1038/nn.3053.
  Compton, D. R., Aceto, M. D., Lowe, J., & Martin, B. R. (1996). In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): Inhibition of delta 9‐tetrahydrocannabinol‐induced responses and apparent agonist activity. The Journal of Pharmacology and Experimental Therapeutics, 277, 586–594.
  Compton, D. R., Rice, K. C., De Costa, B. R., Razdan, R. K., Melvin, L. S., Johnson, M. R., & Martin, B. R. (1993). Cannabinoid structure‐activity relationships: Correlation of receptor binding and in vivo activities. The Journal of Pharmacology and Experimental Therapeutics, 265, 218–226.
  DeLong, G. T., Wolf, C. E., Poklis, A., & Lichtman, A. H. (2010). Pharmacological evaluation of the natural constituent of Cannabis sativa, cannabichromene and its modulation by Δ(9)‐tetrahydrocannabinol. Drug and Alcohol Dependence, 112, 126–133. doi: 10.1016/j.drugalcdep.2010.05.019.
  Duverneuil‐Mayer, C., Charlier, P., Abe, E., Lorin de la Grandmaison, G., Grassin‐Delyle, S., & Alvarez, J.‐C. (2011). Kinetic study of Δ9‐tetrahydrocannabinol, its metabolites, cannabidiol and cannabinol in the blood and brain of mice. Application to humans. Annales de Toxicologie Analytique, 23, 193–204. doi: 10.1051/ata/2011128.
  Fride, E., Perchuk, A., Hall, F. S., Uhl, G. R., & Onaivi, E. S. (2006). Behavioral methods in cannabinoid research. Methods in Molecular Medicine, 123, 269–290. doi: 10.1385/1‐59259‐999‐0:269.
  Han, J., Kesner, P., Metna‐Laurent, M., Duan, T., Xu, L., Georges, F., … Zhang, X. (2012). Acute cannabinoids impair working memory through Astroglial CB1 receptor modulation of hippocampal LTD. Cell, 148, 1039–1050. doi: 10.1016/j.cell.2012.01.037.
  Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W. A., … Pertwee, R. G. (2002). International union of pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacological Reviews, 54, 161–202. doi: 10.1124/pr.54.2.161.
  Martin, B. R. (1986). Cellular effects of cannabinoids. Pharmacological Reviews, 38, 45–74.
  Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature, 346, 561–564. doi: 10.1038/346561a0.
  McLaughlin, P. J., Thakur, G. A., Vemuri, V. K., McClure, E. D., Brown, C. M., Winston, K. M., … Salamone, J. D. (2013). Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054. Pharmacology, Biochemistry, and Behavior, 109, 16–22. doi: 10.1016/j.pbb.2013.04.011.
  Monory, K., Blaudzun, H., Massa, F., Kaiser, N., Lemberger, T., Schütz, G., … Marsicano, G. (2007). Genetic dissection of behavioural and autonomic effects of Δ9‐tetrahydrocannabinol in mice. PLoS Biology, 5, e269. doi: 10.1371/journal.pbio.0050269.
  Pacher, P., & Kunos, G. (2013). Modulating the endocannabinoid system in human health and disease–successes and failures. The FEBS Journal, 280, 1918–1943. doi: 10.1111/febs.12260.
  Pertwee, R. G. (2012). Targeting the endocannabinoid system with cannabinoid receptor agonists: Pharmacological strategies and therapeutic possibilities. Philosophical Transactions of the Royal Society, Series B: Biological Sciences, 367, 3353–3363. doi: 10.1098/rstb.2011.0381.
  Picone, R. P., & Kendall, D. A. (2015). Minireview: From the bench, toward the clinic: Therapeutic opportunities for cannabinoid receptor modulation. Molecular Endocrinology, 29, 801–813. doi: 10.1210/me.2015‐1062.
  Rahn, E. J., Thakur, G. A., Wood, J. A. T., Zvonok, A. M., Makriyannis, A., & Hohmann, A. G. (2011). Pharmacological characterization of AM1710, a putative cannabinoid CB2 agonist from the cannabilactone class: Antinociception without central nervous system side‐effects. Pharmacology Biochemistry and Behavior, 98, 493–502. doi: 10.1016/j.pbb.2011.02.024.
  Rinaldi‐Carmona, M., Barth, F., Héaulme, M., Shire, D., Calandra, B., Congy, C., … Caput, D. (1994). SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Letters, 350, 240–244. doi: 10.1016/0014‐5793(94)00773‐X.
  Vallée, M., Vitiello, S., Bellocchio, L., Hebert‐Chatelain, E., Monlezun, S., Martin‐Garcia, E., … Piazza, P. V. (2014). Pregnenolone can protect the brain from cannabis intoxication. Science, 343, 94–98. doi: 10.1126/science.1243985.
  Varvel, S. A. (2005). 9‐Tetrahydrocannbinol accounts for the antinociceptive, hypothermic, and cataleptic effects of marijuana in mice. Journal of Pharmacology and Experimental Therapeutics, 314, 329–337. doi: 10.1124/jpet.104.080739.
  Wiley, J. (2003). Cannabinoid pharmacological properties common to other centrally acting drugs. European Journal of Pharmacology, 471, 185–193. doi: 10.1016/S0014‐2999(03)01856‐9.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library