No effect of albinism on sedative-hypnotic sensitivity to ethanol and anesthetics.
BACKGROUND
Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS) recombinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (ISS) intercrosses have found genetic linkage between Tyr albinism (c/c) and differential sensitivity to sedative-hypnotic doses of ethanol and general anesthetics. This linkage could be due to a gene or genes near Tyr or Tyr itself. With regard to the latter possibility, the absence of tyrosinase activity (encoded by Tyr) in albinos could alter tyrosine availability and thus the rate-limiting step in catecholamine synthesis. In addition, albinism is associated with altered brain development that could have pleiotropic effects on behavior. Therefore, in this study, we asked whether albinism affects sedative-hypnotic sensitivity.


METHODS
Loss of righting reflex (LORR) duration was measured using doses of ethanol (4.1 g/kg), pentobarbital (70 mg/kg), isoflurane (2 g/kg), and etomidate (20 mg/kg) that were previously associated with differential sensitivity of albino versus nonalbino mice. Tyr transgenics (c/c, Tg(Tyr+)) were backcrossed to ISS (c/c) to compare pigmented (c/c, Tg(Tyr+)) and albino (c/c) mice in the context of an ISS-like background. ISS was also crossed with C57BL/6 (B6) mice heterozygous for a spontaneous albino mutation (c2j) to compare pigmented (c/+) and albino (c/c2j) mice. Pigmented B6 (c2j/+ and +/+) and albino B6 (c2j/c2j) mice were also compared (pentobarbital).


RESULTS
For each sedative hypnotic, albinism had no effect on LORR duration. Each expected difference was ruled out at the 95% or 99% confidence level. For each sedative hypnotic, males were more sensitive than females even though the effect size was usually smaller than the expected albino effect size, arguing empirically that the inability to detect an albino effect was not due to systematic error or an insufficient number of mice.


CONCLUSIONS
We conclude that the differential sensitivity associated with albinism is most likely due to a gene or genes near Tyr rather than Tyr itself.
Institute for Behavioral Genetics, University of Colorado, Boulder 80309-0447, USA. rikke@colorado.edu
B A
BA
Rikke
V J
VJ
Simpson
L
L
Montoliu
T E
TE
Johnson
D000417:Albinism / Q000235:genetics / Q000503:physiopathology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D003433:Crosses, Genetic; D000431:Ethanol / Q000494:pharmacology*; D005045:Etomidate / Q000494:pharmacology; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010424:Pentobarbital / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D012018:Reflex / Q000187:drug effects
D000777:Anesthetics; D006993:Hypnotics and Sedatives; D000431:Ethanol; D007530:Isoflurane; D010424:Pentobarbital; D005045:Etomidate