Just add water: cannabinoid discrimination in a water T-maze with FAAH(-/-) and FAAH(+/+) mice

Behav Pharmacol. 2016 Aug;27(5):479-84. doi: 10.1097/FBP.0000000000000228.

Abstract

Incomplete overlap in the discriminative stimulus effects of Δ-tetrahydrocannabinol (THC) and the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol has been reported in food-reinforced tasks. The aim of this study was to examine cannabinoid discriminative stimulus effects in a nonappetitive procedure. Adult male mice lacking the gene for AEA's major metabolic enzyme, fatty acid amide hydrolase (FAAH), and FAAH mice were trained to discriminate THC or AEA in a water T-maze, in which the response was swimming to an escape platform on the injection-appropriate side. JZL184, a monoacylglycerol lipase inhibitor, was also tested. FAAH mice showed faster acquisition than FAAH mice. THC and AEA fully substituted, with only minor cross-procedure potency variations. Incomplete substitution of JZL184 was observed in THC-trained FAAH mice in the water-maze task, as contrasted with full substitution in a food-reinforced nose-poke procedure. Stress-induced changes in AEA and/or 2-arachidonoylglycerol concentrations in the brain may have mediated this attenuation. JZL184 also partially substituted in AEA-trained FAAH mice in the water maze, suggesting incomplete overlap in the stimulus effects of AEA and JZL184. Through the use of a novel water-maze procedure, the present study supports the work of previous behavioral pharmacologists in showing the robustness of the discrimination paradigm.

MeSH terms

  • Amidohydrolases / genetics*
  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acids / pharmacology*
  • Benzodioxoles / pharmacology
  • Brain / metabolism
  • Discrimination, Psychological / drug effects
  • Dronabinol / pharmacology*
  • Endocannabinoids / pharmacology*
  • Glycerides / pharmacology*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Piperidines / pharmacology
  • Polyunsaturated Alkamides / pharmacology*
  • Water

Substances

  • Arachidonic Acids
  • Benzodioxoles
  • Endocannabinoids
  • Glycerides
  • JZL 184
  • Piperidines
  • Polyunsaturated Alkamides
  • Water
  • Dronabinol
  • glyceryl 2-arachidonate
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide