No effect of albinism on sedative-hypnotic sensitivity to ethanol and anesthetics

Background: Studies using the long-sleep (LS) X short-sleep (SS) (LSXSS) re combinant inbred mice and inbred long-sleep (ILS) by inbred short-sleep (IS S) intercrosses have found generic linkage between SI albinism (cic) and di fferential sensitivity to sedative-hypnotic doses of ethanol and general an esthetics. This linkage could be due to a gene or genes near Tyr or Tyr its elf. With regard to the latter possibility, the absence of tyrosinase activ ity (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 effe cts on behavior. Therefore, in this study, we asked whether albinism affect s sedative-hypnotic sensitivity. Methods: Loss of righting reflex (LORR) duration was measured using doses o f ethanol (4.1 g/kg), pentobarbital (70 mg/kg), isoflurane (2 g/kg), and et omidate (20 mg/kg) that were previously associated with differential sensit ivity of albino versus nonalbino mice. Tyr transgenics (c/c, Tg(Tyr+)) were backcrossed to ISS (CIC) to compare pigmented (cic, Tg(Tyr+)) and albino ( cic) mice in the context of an ISS-like background. ISS was also crossed wi th C57BL/6 (B6) mice heterozygous for a spontaneous albino mutation (c(2j)) to compare pigmented (c/+) and albino (c/c(2j)) mice. Pigmented B6 (c(2j)/ + and +/+) and albino B6 (c(2j)/c(2j)) mice were also compared (pentobarbit al). Results: For each sedative hypnotic, albinism had no effect on LORR duratio n. Each expected difference was ruled out at the 95% or 99% confidence leve l. 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. Conclusion: We conclude that the differential sensitivity associated with a lbinism is most likely due to a gene or genes near Tyr rather than Tyr itse lf.