The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat

Abstract

Rationale 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. Materials and 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.

Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action

“…106 A similar effect of CBD on anticipatory nausea was observed with a rat model of nausea (conditioned gaping). 107 These results support anecdotal claims that marijuana may suppress the expression of anticipatory nausea experienced by chemotherapy patients, resistant to current anti-nausea treatments.…”

Second-order conditioning of LiCl-induced gaping with flavor and contextual cues

“…Morrow et al, 1998), the expression of contextually-elicited conditioned gaping in both rats and shrews is not modified by pre-treatment with classical antiemetics such as ondansetron (Limebeer et al, 2006;Parker et al, 2006;Parker & Kemp, 2001;Rock et al, 2014). On the other hand, cannabinoid compounds, including the psychoactive Δ 9 -tetrahydrocannabinol (THC), but also non-psychoactive cannabidiol and cannabidiolic acid, are highly effective in reducing these behaviors reflective of anticipatory nausea Rock et al, 2008Rock et al, , 2014. Although such manipulations were not assessed in the current study, these compounds would be likely to reduce the establishment and/or expression of second order conditioning, as well.…”

Chemical Probes of Endocannabinoid Metabolism

“…treatment suppressed conditioned gaping, a model of nausea, in response to odors (Rock et al, 2008) or tastes (Cross-Mellor et al, 2007) that had been previously paired with the emetic stimulant lithium chloride (LiCl) by CB1-dependent mechanisms. In contrast, JZL184 treatment (40 mg/kg i.p.)…”