The relationship between PROP and ethanol preferences: an evaluation of 4 inbred mouse strains

Ethanol's taste attributes undoubtedly contribute to the development of drug preference. Ethanol's taste is both sweet and bitter. Taster status for bitter 6-n-propylthiouracil (PROP) has been proposed as a genetic marker for alcoholism; however, human results are conflicting. We collected preference scores for both tastants in 4 mouse strains selected on the basis of previously reported taste preference, with the generally accepted idea that inbred mice show minimal within-strain variation. Eighty-eight male mice (22 per strain) participated. The strains were as follows: C57BL/6J, ethanol preferring; BALB/cJ, ethanol avoiding; SWR/J, PROP avoiding; and C3HeB/FeJ, PROP neutral. Using a brief-access (1-min trials) 2-bottle preference test, we assessed the taste response of each strain to PROP and ethanol on separate days. Although PROP avoiding versus neutral mice could be segregated into significantly different populations, this was not the case for ethanol avoiding versus preferring mice, and all strains showed high variability. On average, only BALB/cJ, SWR/J, and C3HeB/FeJ mice conformed to their literature-reported preferences; nonetheless, there were a substantial number of discordant animals. C57BL/6J did not conform to previous results, indicating that they are ethanol preferring. Finally, we did not observe a significant relationship between PROP and ethanol preferences across strains. The high variability per strain and the number of animals in disagreement with their respective literature-reported preference raise concerns regarding their utility for investigations underlying mechanisms of taste-mediated ingestive responses. Absent postingestive consequences, the brief-access results suggest a possible degree of previously masked polymorphisms in taste preferences or a more recent drift in underlying genetic factors. The absence of a relationship between PROP and ethanol indicates that the bitter quality in ethanol may be more highly related to other bitter compounds that are mediated by different genetic influences.