Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines.
Previous studies have identified quantitative trait loci (QTL) in the inbred high and low alcohol-sensitive rat (IHAS1 and ILAS1) strains. The original development of the strains involved selection for ethanol sensitivity based on duration of the loss of the righting reflex (LORR) after a standard dose of ethanol. This paper confirms some of these QTL using a short-term selection procedure based on the difference between the blood ethanol level at LORR and regain of the righting response. An F(2) population of rats was developed by a reciprocal cross of IHAS1 and ILAS1 rats. Selection for five generations was carried out using delta-blood ethanol concentration (dBEC) as the selection trait, where dBEC=BECLR (BEC at loss of righting reflex)-BECRR (BEC at regain of righting reflex). The lines were labeled tolerant (TOL) or sensitive (SENS). Approximately one-third of the offspring for each generation in each line were genotyped using DNA markers that had been previously found to be linked to QTL on chromosomes 1, 2, 5, 12, and 13. By the fifth generation of selection, the lines showed a very large difference in dBEC, BECRR, and duration of LORR; BECLR showed little segregation during the selection, and latency to lose the righting reflex showed none. IHAS allele frequency increased in the SENS line for markers on chromosomes 1, 5, 12, and 13 while ILAS allele frequency increased in the TOL line. These results were in good agreement with the two previous QTL studies. On chromosome 2, the selection resulted in an accumulation of ILAS alleles in both lines. This study provides independent confirmation of the location of QTL on chromosomes 1, 5, 12, and 13 for ethanol sensitivity. It also suggests that genetic differences in duration of LORR are mediated primarily by the dBEC phenotype.
Department of Pharmaceutical Sciences, University of Colorado at Denver and Health Sciences Center, Campus Box C238, 4200 East Ninth Avenue, Denver, CO 80262, USA. richard.radcliffe@uhsc.edu
Richard A
RA
Radcliffe
Pequita
P
Bludeau
Xin-Sheng
XS
Deng
V Gene
VG
Erwin
Richard A
RA
Deitrich
D000428:Alcohol Drinking / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D000437:Alcoholism / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D004361:Drug Tolerance / Q000235:genetics*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D009043:Motor Activity / Q000187:drug effects*; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time; D012018:Reflex / Q000187:drug effects; D012641:Selection, Genetic
D002492:Central Nervous System Depressants; D000431:Ethanol