Comprehensive behavioral analysis of mice repeatedly treated with propofol

Propofol, known as “milk of anesthesia”, is used for the induction and maintenance of anesthesia. Recently, propofol has attracted increasing concerns about its safety and abuse potential because of its psychostimulant effects such as euphoria and sexual hallucinations. Previous reports focused on the effects of postoperative and neonatal exposure to propofol. However, the lasting effects of repetitive propofol administration during adulthood have not been well investigated. It is conceivable that prolonged use of propofol affects brain function and the behavioral characteristics of the abused patient. Thus, we performed a comprehensive behavioral analysis of mice exposed to propofol. Adult male C57BL/6J mice were repeatedly administered with propofol (20 or 80 mg/kg/day i.p.), intralipos (vehicle control), or saline only once a day for seven days. We then performed a behavioral test battery to evaluate various behaviors. Afterwards, we resumed the propofol treatment for three days and subsequently conducted contextual and cued fear conditioning tests. In the three‐chamber social approach test, propofol treatment attenuated social novelty preference in mice. In the fear conditioning test, high dose-treated mice exhibited impaired long-term cued-dependent memory retention. In the rotarod test, propofol- and intralipos-treated mice tended to have decreased motor coordination than the saline-treated mice. Our results demonstrated that repetitive propofol treatment has the potential to induce some behavioral changes in mice. Additionally, the solvent itself might have effects different from that of propofol. Our findings provide basic data on the safe use and risk of propofol abuse. Highlights Propofol, known as “milk of anesthesia”, has attracted increasing concerns about its safety and abuse potential. The lasting effects of repetitive propofol administration during adulthood have not been well investigated. To clarify the effects of repetitive propofol use on brain function and behavioral characteristics, we performed a comprehensive behavioral analysis of mice exposed to propofol. In this study, propofol treatment attenuated the social novelty preference and the performance of the cued long-term memory task in mice. Additionally, treatment with propofol and intralipos tended to induce decreased motor coordination. Our results demonstrated that repetitive propofol treatment has the potential to induce some behavioral changes in mice. Furthermore, the solvent itself might have effects different from that of propofol. Our findings provide basic data for the safe use and risk of propofol abuse.