Open AccessNausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018
Author(s) -
Marieka V. DeVuono,
Kelly M. Hrelja,
Gavin N Petrie,
Cheryl L. Limebeer,
Erin M. Rock,
Matthew N. Hill,
Linda A. Parker
Publication year - 2020
Publication title -
cannabis and cannabinoid research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.156
H-Index - 17
eISSN - 2578-5125
pISSN - 2378-8763
DOI - 10.1089/can.2019.0103
Subject(s) - rimonabant , cannabinoid , cannabinoid receptor , pharmacology , chemistry , synthetic cannabinoids , nausea , agonist , cannabinoid receptor antagonist , inverse agonist , taste aversion , medicine , anesthesia , receptor , biochemistry , taste
Cannabinoid hyperemesis syndrome is becoming a more prominently reported side effect of cannabis containing high-dose Δ 9 -tetrahydrocannabinol (THC) and designer cannabinoid drugs such as "Spice." One active ingredient that has been found in "Spice" is 1-pentyl-3-(1-naphthoyl)indole (JWH-018), a synthetic full agonist of the cannabinoid 1 (CB 1 ) receptor. In this study, we evaluated the potential of different doses of JWH-018 to produce conditioned gaping in rats, an index of nausea. Materials and Methods: Rats received 3 daily conditioning trials in which saccharin was paired with JWH-018 (0.0, 0.1, 1, and 3 mg/kg, intraperitoneal [i.p.]). Then the potential of pretreatment with the CB 1 antagonist, rimonabant (SR), to prevent JWH-018-induced conditioned gaping was determined. To begin to understand the potential mechanism underlying JWH-018-induced nausea, serum collected from trunk blood was subjected to a corticosterone (CORT) analysis in rats receiving three daily injections with vehicle (VEH) or JWH-018 (3 mg/kg). Results: At doses of 1 and 3 mg/kg (i.p.), JWH-018 produced nausea-like conditioned gaping reactions. The conditioned gaping produced by 3 mg/kg JWH-018 was reversed by pretreatment with rimonabant, which did not modify gaping on its own. Treatment with JWH-018 elevated serum CORT levels compared to vehicle-treated rats. Conclusions: As we have previously reported with high-dose THC, JWH-018 produced conditioned gaping in rats, reflective of a nausea effect mediated by its action on CB 1 receptors and accompanied by elevated CORT, reflective of hypothalamic-pituitary-adrenal (HPA) activation.