title: The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat.
abstract: BACKGROUND
  Anticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined.
  
  
  OBJECTIVE
  The potential of cannabidiol (CBD) and the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (URB) to reduce conditioned gaping in rats were evaluated.
  
  
  METHODS
  In each experiment, rats received four conditioning trials in which they were injected with lithium chloride immediately before placement in a distinctive odor-laced context. During testing, in experiment 1, rats were injected with vehicle (VEH), 1, 5 or 10 mg/kg CBD 30 min before placement in the context previously paired with nausea and in experiment 2, rats were injected with VEH, 0.1 or 0.3 mg/kg URB 2 h before placement in the context. Additional groups evaluated the ability of the CB(1) antagonist/inverse agonist, SR141716A, to reverse the suppressive effects of URB. Experiment 3 measured the potential of URB to interfere with the establishment of conditioned gaping.
  
  
  RESULTS
  When administered before testing, CBD (1 and 5, but not 10 mg/kg) and URB (0.3, but not 0.1 mg/kg) suppressed conditioned gaping. The effect of URB was reversed by pre-treatment with the CB(1) antagonist/inverse agonist, SR141716A. When administered before conditioning, URB also interfered with the establishment of conditioned gaping.
  
  
  CONCLUSIONS
  Manipulations of the EC system may have therapeutic potential in the treatment of AN.
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Rock
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Limebeer
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Linda A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects; D001549:Benzamides / Q000494:pharmacology*; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018021:Lithium Chloride; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D014840:Vomiting, Anticipatory / Q000139:chemically induced / Q000188:drug therapy*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000932:Antiemetics; D000970:Antineoplastic Agents; D001549:Benzamides; D002185:Cannabidiol; D002219:Carbamates; D018021:Lithium Chloride; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester