Propofol-induced ataxia and hypnosis in rat lines selected for differential alcohol sensitivity.
An alcohol-sensitive rat line, selectively bred for high sensitivity to ethanol-induced motor impairment, also exhibits greater sensitivity to gamma-aminobutyric acid type A (GABAA) receptor agonists, such as benzodiazepines and barbiturates, than an alcohol-insensitive rat line. We have investigated whether this difference was also maintained for the most recent intravenous anaesthetic, propofol. Propofol (100 mg/kg, intraperitoneally) induced similar sleep times and produced identical plasma propofol concentrations in alcohol-sensitive and alcohol-insensitive rat lines. At lower doses (50 and 75, but not 25 mg/kg), propofol produced a greater motor impairment in a tilting plane test in alcohol-sensitive than alcohol-insensitive rats shortly after the injection. Binding of a convulsant, [35S]t-butylbicyclophosphorothionate, to cerebellar and cerebrocortical GABAA receptors in the presence of 2 microM GABA was similarly affected by low micromolar propofol concentrations in both rat lines, while in the absence of GABA, propofol was slightly less potent in the alcohol-sensitive than alcohol-insensitive line. These data indicate that alcohol-sensitive rats show transiently enhanced sensitivity to an ataxic, but not to a hypnotic dose of propofol, which cannot be explained by sensitivity differences to propofol in GABAA receptors determined in a binding assay using brain membrane homogenates.
Yildirim
Y
Y
Department of Anaesthesiology, Helsinki University Central Hospital, Finland.
Niemi
L
L
Wong
G
G
Korpi
E R
ER
Rosenberg
P H
PH
D000428:Alcohol Drinking / Q000235:genetics*; D018681:Anesthetics, General / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001259:Ataxia / Q000139:chemically induced*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015742:Propofol / Q000493:pharmacokinetics / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D013045:Species Specificity; D013462:Sulfur Radioisotopes; D013997:Time Factors
D018681:Anesthetics, General; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D013462:Sulfur Radioisotopes; C037476:tert-butylbicyclophosphorothionate; D015742:Propofol