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Effect of hypnotics on mice genetically selected for sensitivity to ethanol
Pharmacology, Biochemistry, and Behavior
|June 1, 1976
Summary
Mice selectively bred for ethanol sleep differences show varying sensitivity to certain alcohols but not to other hypnotics. This suggests specific central nervous system (CNS) pathways are involved in ethanol
Area of Science:
- Pharmacology
- Neuroscience
- Genetics
Background:
- Two mouse lines (SS and LS) were selectively bred for differing sleep durations following ethanol administration.
- Previous studies indicated identical ethanol blood disappearance rates but different ED50 values for loss of righting response between SS and LS mice.
Purpose of the Study:
- To investigate the central nervous system (CNS) sensitivity differences between SS and LS mice using various depressant agents.
- To determine if observed differences in ethanol sensitivity extend to other hypnotic and anesthetic compounds.
Main Methods:
- Administered ethanol, methanol, butanol, t-butanol, sodium pentobarbital, and ether to SS and LS mice.
- Measured ED50 (median effective dose) for loss of righting response and determined LD50 (median lethal dose) for ethanol.
- Recorded sleep times following administration of ethanol and other hypnotic agents (pentobarbital, chloral hydrate, trichloroethanol, paraldehyde).
Main Results:
- ED50 values for ethanol-induced loss of righting response were significantly different (SS: 3.64 g/kg, LS: 1.65 g/kg).
- Mean sleep times differed greatly (SS: 367 sec, LS: 9342 sec), while ethanol LD50 values were similar (SS: 4.8 g/kg, LS: 4.5 g/kg).
- SS mice required approximately twice the dose of methanol, butanol, and t-butanol for loss of righting response compared to LS mice.
- ED50 values for sodium pentobarbital and ether were virtually identical between the two lines.
- Sleep times after administration of pentobarbital, chloral hydrate, trichloroethanol, and paraldehyde were not significantly different.
Conclusions:
- The SS and LS mouse lines exhibit distinct CNS sensitivity to ethanol, methanol, butanol, and t-butanol.
- These findings imply that the genetic differences influencing ethanol sensitivity in these lines do not affect sensitivity to other tested hypnotic agents.
- Further research on metabolic rates and brain levels is needed to confirm CNS sensitivity to other depressants.