Role of the stress response and the endocannabinoid system in Δ
Dysregulation of the endocannabinoid (eCB) system by high doses of Δ Using the conditioned gaping model of nausea, we aimed to determine if pre-treatments that interfere with stress, or an anti-emetic drug, interfere with THC-induced nausea in male rats. The corticotropin-releasing hormone (CRH) antagonist, antalarmin, was given to inhibit the HPA axis during conditioning. Since eCBs inhibit stress, MJN110 (which elevates 2-arachidonylglycerol (2-AG)) and URB597 (which elevates anandamide (AEA)) were also tested. Propranolol (β-adrenergic antagonist) and WAY-100635 (5-HT Antalarmin (10 and 20 mgkg), MJN110 (10 mgkg), URB597 (0.3 mgkg), propranolol (2.5 and 5 mgkg), WAY-100635 (0.5 mgkg), and chlordiazepoxide (5 mgkg) interfered with THC-induced conditioned gaping, but the anti-emetic ondansetron (0.1 and 0.01 mgkg) did not. THC produced significantly higher CORT levels at 10 mgkg than at 0.0 and 0.5 mgkg THC. Treatments that interfere with the stress response also inhibit THC-induced conditioned gaping, but a typical anti-emetic drug does not, supporting the hypothesis that THC-induced nausea, and CHS, is a result of a dysregulated stress response.