Pain L, Oberling P, Launoy A, Di Scala G
Service d'Anesthésie Réanimation Chirurgicale and U405 INSERM, Strasbourg, France.
Anesthesiology. 1999 Jan;90(1):191-6. doi: 10.1097/00000542-199901000-00025.
The effect of propofol on anxiety has not been well studied. In humans, such investigations are confused by the fact that sedation often coexists with anxiolysis. Therefore, the authors evaluated the effects of minimal sedation with propofol in rats placed in an innate anxiogenic situation, the elevated plus-shaped maze.
In experiment 1, spontaneous locomotor activity was determined in rats as a measure of sedative effect induced by propofol (0-9 mg/kg administered intraperitoneally). In experiment 2, groups of rats received propofol (0-9 mg/kg) or diazepam (0-2 mg/kg) and then were placed on a plus-shaped maze elevated above the ground that was composed of two opposite closed arms and two opposite open arms. On an initial exposure to the maze, undrugged rats avoid the open arms, with the number of entries into and time spent within the open arms constituting approximately 20% of their total activity. This reflects normal anxiety in a rodent for any elevated open platform.
In experiment 1, 0-9 mg/kg propofol did not alter spontaneous activity in rats. In experiment 2, propofol and diazepam significantly increased the number of entries into and the time spent within the open arms. Propofol at a dose of 9 mg/kg significantly increased the rats' level of exploration of the open arms to about 50% of all exploratory activity, and a similar observation was made with 2 mg/kg diazepam.
In a standard animal model, propofol has anxiolytic properties at doses that do not produce sedation.
丙泊酚对焦虑的影响尚未得到充分研究。在人类中,由于镇静作用常与抗焦虑作用并存,此类研究受到干扰。因此,作者评估了在处于先天性焦虑诱发环境(高架十字迷宫)中的大鼠身上,使用丙泊酚进行最小程度镇静的效果。
在实验1中,测定大鼠的自发运动活动,以此作为丙泊酚(腹腔注射0 - 9毫克/千克)诱导的镇静效果指标。在实验2中,将大鼠分组,分别给予丙泊酚(0 - 9毫克/千克)或地西泮(0 - 2毫克/千克),然后将它们置于高于地面的十字迷宫中,该迷宫由两个相对的封闭臂和两个相对的开放臂组成。在初次接触迷宫时,未用药的大鼠会避开开放臂,进入开放臂的次数和在开放臂内停留的时间约占其总活动量的20%。这反映了啮齿动物对任何高架开放平台的正常焦虑。
在实验1中,0 - 9毫克/千克的丙泊酚未改变大鼠的自发活动。在实验2中,丙泊酚和地西泮显著增加了进入开放臂的次数和在开放臂内停留的时间。9毫克/千克剂量的丙泊酚显著将大鼠对开放臂的探索水平提高到所有探索活动的约50%,2毫克/千克地西泮也有类似观察结果。
在标准动物模型中,丙泊酚在不产生镇静作用的剂量下具有抗焦虑特性。