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

Abstract

This study aimed to elucidate the mechanism underlying tolerance to the sedative effects of propofol, focusing on cannabinoid 1 (CB1) receptor regulation. Male Wistar rats received continuous propofol infusion (30–40 mg/kg/h) for 1, 2, 4, or 12 h prior to tissue collection. Brain regions including the cortex, hippocampus, striatum, brain stem, and cerebellum were analyzed. Changes in CB1 receptor mRNA transcript abundance were assessed using semi-quantitative PCR. Across all examined regions, CB1 receptor mRNA levels showed a time-dependent decrease following propofol administration. Reductions were detectable as early as 1 h and became more pronounced at 4 and 12 h. This downregulation was consistently observed across multiple brain regions, suggesting a widespread effect rather than region-specific modulation. These findings suggest that continuous propofol exposure leads to significant downregulation of CB1 receptor expression, which may contribute to receptor desensitization and the development of tolerance to its sedative effects. Modulation of the endocannabinoid system may therefore play a key role in propofol-induced tolerance.