Conditioned gaping produced by high dose Δ9-tetrahydracannabinol: Dysregulation of the hypothalamic endocannabinoid system

DeVuono, Marieka V.; Hrelja, Kelly M.; Sabaziotis, Lauren; Rajna, Alex; Rock, Erin M.; Limebeer, Cheryl L.; Mutch, David M.; Parker, Linda A.

doi:10.1016/j.neuropharm.2018.08.039

Cited by 11 publications

(15 citation statements)

References 85 publications

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“…Consistent with high-dose THC, 9 JWH-018 produced a dose-dependent increase in nausea-induced conditioned gaping reactions in rats at i.p. doses of 1 and 3 mg/kg, but not 0.1 mg/kg.…”

Section: Discussionmentioning

confidence: 69%

“…), but not a low dose (0.5 mg/kg), produce conditioned gaping in the TR test in rats. 9 Nausea is a common side effect of Spice use in humans, which is reported more often than with THC use. 22 JWH-018 is a full agonist at the CB 1 and is more potent and efficacious than the partial CB 1 receptor agonist, THC; therefore, it is not surprising that JWH-018 would produce conditioned gaping at lower doses than THC (5 and 10 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

“…A total of 80 naive male Sprague Dawley rats obtained from Charles River Laboratories (St Constant, Canada) were used in all experiments. Rats were single housed and maintained as described by DeVuono et al 9 On the first day of conditioning, for experiments 1 and 2, rats weighed between 273 and 403 g and between 262 and 324 g on the day of blood collection for experiment 4. All experimental manipulations occurred during the dark phase of the cycle.…”

Section: Subjectsmentioning

confidence: 99%

“…Behavioral procedures Experiment 1: dose-response potential of JWH-018 to produce conditioned gaping. As reported by DeVuono et al, 9 following 3 days of recovery from intraoral surgery, the rats were adapted to the TR chamber. Water was infused into their intraoral cannulae through an infusion pump for 2 min at the rate of 1 mL/min.…”

Section: Intraoral Cannulation Surgerymentioning

confidence: 99%

“…[1][2][3] These human reports are consistent with laboratory findings using animal models, as high doses of the partial agonist of the cannabinoid 1 (CB 1 ) receptor, D 9 -tetrahydrocannabinol (THC), produce vomiting in shrews, 4,5 monkeys, 6 cats, 7 and dogs, 8 and nausea-like conditioned gaping in rats. 9 CHS can also be caused by use of ''Spice,'' a group of designer drugs that contain synthetic cannabinoids, such as the potent 1-pentyl-3-(1-naphthoyl)indole ( JWH-018). [10][11][12][13][14][15] Unlike THC, JWH-018 acts as a full agonist of CB 1 .…”

Section: Introductionmentioning

confidence: 99%

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

DeVuono

Hrelja

Petrie

et al. 2020

Cannabis and Cannabinoid Research

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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.

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“…Consistent with high-dose THC, 9 JWH-018 produced a dose-dependent increase in nausea-induced conditioned gaping reactions in rats at i.p. doses of 1 and 3 mg/kg, but not 0.1 mg/kg.…”

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Section: Intraoral Cannulation Surgerymentioning

confidence: 99%