Effects of propofol on the mRNA transcript abundance of CB1 receptors in rat brain

Background: Propofol is used for the induction and maintenance of anaesthesia and long-term sedation. Prolonged continuous administration of propofol may induce tolerance to its sedative effects; however, the exact mechanism underlying this tolerance remains unclear. Propofol enhances the concentration of anandamide, an endogenous cannabinoid, by inhibiting fatty acid amide hydrolase, which suggests a role of the cannabinoid system in anaesthetic and sedative actions of propofol. Cannabinoid 1 (CB1) receptors reportedly cause desensitization due to long-term exposure to ligands. We hypothesized that CB1 receptors are involved in the development of tolerance to the sedative effects of propofol. Methods: Male Wistar rats were administered propofol at doses of 30–40 mg/kg/h for 1, 2, 4, and 12 h prior to decapitation. Then, tissue sections were obtained from the cortex, hippocampus, striatum, brain stem, and cerebellum. We investigated changes in mRNA transcript abundance of CB1 receptors using a semi-quantitative PCR analysis. Results: After 1–12 h of propofol administration, the mRNA transcript abundance of CB1 receptors significantly decreased (45.8%–80.1%) in all brain regions (P < 0.05). Conclusions: The results suggest the following mechanism: an increased concentration of anandamide within the brain may be involved in the decrease of mRNA transcript abundance of CB1 receptor, resulting in the development of tolerance to the sedative effects of propofol.