Psychopharmacology 2020-May
Role of the stress response and the endocannabinoid system in Δ9-tetrahydrocannabinol (THC)-induced nausea.
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Abstrait
RATIONALE
Dysregulation of the endocannabinoid (eCB) system by high doses of Δ9-tetrahydrocannabinol (THC) is hypothesized to generate a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis contributing to cannabinoid hyperemesis syndrome (CHS).OBJECTIVES AND METHODS
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-HT1A antagonist) attenuate HPA activation by cannabinoids and, therefore, were assessed. In humans, CHS symptoms are not alleviated by anti-emetic drugs, such as ondansetron (5-HT3 antagonist); however, benzodiazepines are effective. Therefore, ondansetron and chlordiazepoxide were tested. To determine if HPA activation by THC is dose-dependent, corticosterone (CORT) was analyzed from serum of rats treated with 0.0, 0.5, or 10 mg/kg THC.