Abstract
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. The potential of cannabidiol (CBD) and the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (URB) to reduce conditioned gaping in rats were evaluated. 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. 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. Manipulations of the EC system may have therapeutic potential in the treatment of AN.
Highlights
Chemotherapy-induced nausea and vomiting can be classified into three categories: (1) acute onset, occurring within 24 h of the initial chemotherapy administration; (2) delayed onset, occurring 24 h to several days after the initial treatment; and (3) anticipatory nausea and vomiting (Jordan et al 2005)
The effect of URB was reversed by pre-treatment with the CB1 antagonist/inverse agonist, SR141716A
After one or more treatment sessions, a conditional association develops between the distinctive contextual cues of the treatment environment and the unconditioned stimulus (US) of chemotherapy treatment that results in the unconditioned response (UR) of post-treatment illness experienced by the patient
Summary
Chemotherapy-induced nausea and vomiting can be classified into three categories: (1) acute onset, occurring within 24 h of the initial chemotherapy administration; (2) delayed onset, occurring 24 h to several days after the initial treatment; and (3) anticipatory nausea and vomiting (Jordan et al 2005). Anticipatory nausea (AN) develops in response to chemotherapy treatments, in which cytotoxic drugs are delivered in the presence of a novel context (hospital sights, sounds, smells and tastes). After one or more treatment sessions, a conditional association develops between the distinctive contextual cues of the treatment environment (conditional stimuli; CS) and the unconditioned stimulus (US) of chemotherapy treatment that results in the unconditioned response (UR) of post-treatment illness experienced by the patient. Subsequent exposure to Psychopharmacology (2008) 196:389–395 the treatment environment (CS) results in the patient experiencing a conditioned response (CR) of nausea and/ or vomiting before initiation of chemotherapy treatment. Once it develops, AN has been reported to be especially refractive to anti-emetic treatment (Morrow et al 1998; Foubert and Vaessen 2005)
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