Propofol produces differences in behavior but not chloride channel function between selected lines of mice

We report differential central nervous system (CNS) sensitivity to propofol between Long Sleep (LS) and Short Sleep (SS) mice, selectively bred for their differential CNS sensitivity to ethanol. Intravenous propofol requirements for loss of righting reflex, or sleep time, were measured to define the extent of this sensitivity. LS mice slept approximately two times longer than SS mice at equal doses. Awakening plasma and brain levels of the SS line were, respectively, two and three times that of the LS line (P < 0.0001). This suggests that the LS and SS sleep time difference is CNS mediated, and that propofol and ethanol may share common genes that determine anesthetic sensitivities. The ethanol effect may be at least partially mediated by gamma-aminobutyric acid-A (GABAA) receptor function. Propofol had no differential effect on GABAA receptor function, as measured by chloride flux in LS and SS brain microsac preparations. Either the GABAA receptor does not mediate propofol sleep time, or qualitative differences cannot be demonstrated using 36Cl- uptake in brain membranes.