title: Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats.
abstract: OBJECTIVE
  To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND).
  
  
  METHODS
  We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined.
  
  
  RESULTS
  CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping.
  
  
  CONCLUSIONS
  CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients.
authors.affiliation: Department of Psychology, University of Guelph, Guelph, ON, Canada.
authors.forename: E M
authors.initials: EM
authors.lastname: Rock
authors.forename: L A
authors.initials: LA
authors.lastname: Parker
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007274:Injections, Intraperitoneal; D018021:Lithium Chloride; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron / Q000008:administration & dosage* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D013649:Taste
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D002186:Cannabinoids; D058829:Serotonin 5-HT1 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D017294:Ondansetron; C006884:cannabidiolic acid; D018021:Lithium Chloride