Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018

Abstract

Introduction: Cannabinoid hyperemesis syndrome is becoming a more prominently reported side effect of cannabis containing high-dose D 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.

Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats

“…Plasma corticosterone levels were determined using an ELISA as previously described, according to the manufacturer's protocol (Cayman Chemical Company, Ann Arbor, Michigan, USA, #500655, RRID: AB_2868564 —for restraint and swim stress cohorts ( Vecchiarelli et al, 2015 ); Arbor Assays, Ann Arbor, Michigan, USA, C#K014–H, RRID: AB_2877626 —for the foot shock stress cohort ( DeVuono et al, 2020 )).…”

Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years

“…In contrast, in the current population of recreational cannabis users, a novel cannabis-induced hyperemesis syndrome has been attributed to ingestion of very high doses of THC. The mechanism is poorly understood, but it has been suggested that prolonged exposure to high doses of THC might down-regulate CB 1 R or otherwise perturb the endogenous regulation of vomiting centers in the brain stem and/or elicit stress mechanisms at the hypothalamic-pituitary axis (Galli et al, 2011;DeVuono et al, 2020). Thus, there may be a "bell-shaped" dose-response curve suggesting multiple mechanisms for the anti-versus pro-nausea/vomiting endpoints.…”

Stroboscopic lighting with intensity synchronized to rotation velocity alleviates motion sickness gastrointestinal symptoms and motor disorders in rats

“…The effects of stroboscopic light synchronized or unsynchronized to the acceleration–deceleration phase of rotation were examined, and the influence of color temperature and lighting intensity was also observed. MS-related gastrointestinal responses were assessed by measuring conditioned gaping and defecation responses due to the absence of vomiting reaction in rodents (Wang et al, 2012 , 2017 ; Zhou et al, 2017 ; Qi et al, 2019 ; Devuono et al, 2020 ). Motor and balance performance were evaluated using spontaneous locomotion test and balance beam test (Manno et al, 2020 ).…”