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Abstract

High and low alcohol preference (HAP and LAP, respectively) mice were created by 10 generations of bidirectional selection for differences in two-bottle choice alcohol consumption. The progenitors used for selection were HS/lbg mice, which are a genetically defined, outbred stock. During selection, mice had 24-h, daily access to 10% alcohol (v/v) and water ad libitum for 30 days and were selected based on the alcohol (g/kg) consumed per day over the entire period. Food was available ad libitum. At S10, line means for alcohol consumption differed greatly, with consumption of over 12 g/kg per day in the HAP mice and less than 2 g/kg per day in the LAP mice. Realized heritability for bidirectional selection was approximately 0.2. Female mice consumed more alcohol than male mice. There were no differences between lines in alcohol elimination rate, nor were there line differences in intake of salt or quinine solutions. However, consumption of saccharin solutions was greater in HAP mice than LAP mice, consistent with previous findings of a genetic correlation between sweet preference and alcohol drinking. Because the mouse genome is relatively well characterized, these selected lines should prove a useful tool for assessment of the genetic basis of, and phenotypes that correlate with, alcohol drinking.

The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice

“…With repeated cycles of continuous-access 2-bottle choice drinking, HAP mice typically increase their ethanol intake and preference over days (Grahame et al, 1999; Matson & Grahame, 2011; Oberlin et al, 2011), and this was generally the case in the current study. Given our previous findings (Fritz et al, 2013), we hypothesized that a prior history of alcohol consumption may enhance the already substantial rapid AFT capacity of HAP2 mice.…”

“…All mice were exposed to the 2-bottle choice drinking procedure, in the same manner in which the lines were selected (Grahame et al, 1999), for 18 days. This duration was chosen because ethanol intake typically plateaus for HAP2 mice by this point (Oberlin et al, 2011).…”

“…These lines typically demonstrate an increase in 10% ethanol intake/preference over days in a continuous-access 2-bottle choice paradigm (Grahame, Li, & Lumeng, 1999; Matson & Grahame, 2011; Oberlin, Best, Matson, Henderson, & Grahame, 2011). Given the already demonstrated impressive rapid AFT capacity in ethanol-naïve HAP mice (Fritz et al, 2013), their capacity to escalate ethanol consumption over days may also be reflective of an enhanced ability for alcohol exposure to positively influence this response.…”

Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis

“…Animal models for alcohol-related traits provide an important opportunity to explore mechanisms responsible for different aspects of the uniquely human disease (1). In particular, selected lines and inbred strains of mice with a divergence in voluntary alcohol drinking represent valuable tools to dissect the genetic components of alcoholism (2,6,8,9, § §). However, each model has different advantages.…”

The multiMiR R package and database: integration of microRNA–target interactions along with their disease and drug associations

“…Brain gene expression was compared between five pairs of mouse strains and selected lines (4–6 mice per strain or line) that showed high and low drinking behaviour (42,43). For all five pairs, the transcript for guanine nucleotide binding protein (G protein), beta 1 subunit (Gnb1) was differentially expressed.…”