Sensitivity to the locomotor stimulant effects of ethanol and allopregnanolone is influenced by common genes.
Allopregnanolone is a neuroactive steroid that, like ethanol (EtOH), has stimulant, anxiolytic, ataxic, and depressant effects. Two experiments tested the hypothesis that sensitivity to the locomotor stimulant effects of these drugs is influenced by a common set of genes. Sensitivity to the locomotor stimulant effects of allopregnanolone was determined in 24 BXD recombinant inbred (RI) strains. Strain means were positively correlated with extant means for EtOH stimulation in 20 of the same strains. Quantitative trait locus (QTL) analysis provisionally identified many loci, including several known to influence sensitivity to EtOH. Sensitivity to allopregnanolone was also measured in FAST and SLOW mice, which were selectively bred for differential locomotor response to EtOH, to determine whether selection has also altered allopregnanolone sensitivity. FAST mice were more sensitive to the stimulant effects of allopregnanolone compared with SLOW mice. These data suggest that sensitivity to the locomotor stimulant effects of these drugs is influenced by common genes.
Palmer
Abraham A
AA
Portland Alcohol Research Center, Oregon Health & Science University, USA.
Miller
Mark N
MN
McKinnon
Carrie S
CS
Phillips
Tamara J
TJ
D000818:Animals; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D009043:Motor Activity / Q000187:drug effects*; D011280:Pregnanolone / Q000494:pharmacology*; D019655:Quantitative Trait, Heritable; D011995:Recombination, Genetic / Q000235:genetics; D013268:Stimulation, Chemical
D000431:Ethanol; D011280:Pregnanolone