Propofol suppresses the sleep state-dependent P13 midlatency auditory evoked potential in the rat

Propofol (2,6-diisopropylphenol) is a widely used anesthetic agent, but its mechanisms of action are poorly understood. In this report, the effects of three dose levels of propofol (5, 7.5, and 10mg/kg) on the amplitude of the vertex-recorded, sleep state-dependent P13 midlatency evoked potential were investigated. The P13 potential is generated, at least in part, by the ascending cholinergic reticular activating system (RAS). The RAS is known to be affected by anesthetic agents. Intravenous injections of propofol were found to reduce the amplitude of the P13 potential in a dose- and time-dependent manner. At 2min post-injection, the mean P13 amplitude was suppressed to 40% of its pre-injection level by the lowest dose, but was suppressed to 10% of pre-injection levels by the two higher doses of propofol. The duration of the suppression of mean P13 potential amplitude was also dose-dependent such that complete recovery occurred by 5min using 5mg/kg, by 15min using 7.5mg/kg and by 30min using 10mg/kg of propofol. Using a paired stimulus paradigm, transient effects on habituation of the P13 potential were observed but only after the highest dose. Thus, one of the mechanisms of propofol may be to affect portions of the RAS which modulate the level of arousal. It may only transiently affect higher systems known to modulate the degree of habituation of responses by the RAS (i.e. processes which modulate habituation and may participate in sensory gating and distractibility).