Differential effects of central nervous system depressants in long-sleep and short-sleep mice

The relative sleep time response of long-sleep (LS) and short-sleep (SS) mice was determined after the i.p. injection of varying doses of several anesthetic agents that vary in lipid solubility. The LS and SS mice were bred selectively for differences in duration of ethanol-induced sleep time. The drugs tested included: several halogenated ethanol derivatives (trifluoro-, trichloro-, tribromo- and dichloroethanol), chloral hydrate, paraldehyde, urethane and the water soluble barbiturates, barbital and phenobarbital. The LS mice slept for a longer time after the i.p. injection of the majority of these drugs than did the SS. As the lipid solubility of the agents increased, the response differential decreased. These data indicate that the LS and SS mice do not differ only in response to alcohols. Rather, they differ in sensitivity to agents that have lipid solubilities which resemble that of ethanol. Furthermore, these data imply that anesthetic agents with low lipid solubility have different mechanisms of action than do anesthetic agents with high lipid solubility.