Compared to C57BL/6J Mice, C57BL/6N Mice Exhibit Reduced Ethanol Consumption That Is Not Due to a Discrepancy in Sweet Taste Perception
Primary author: Talia Thuet
Co-author(s): Kevin Douglas
Primary college/unit: College of Veterinary Medicine
DBA/2J (D2) and C57BL/6J (B6J) mice are widely used as models for low and high ethanol (EtOH) consumption genotypes respectively. However, a key determinant of low EtOH consumption in D2 mice is taste-aversion to EtOH, which precludes voluntary consumption to neurologically active concentrations of EtOH. This phenomenon is explained in part by D2 mice having an allele of the sac locus which encodes a sweet taste receptor with reduced responsivity to sweet compounds like saccharin, sucrose, and EtOH. Furthermore, vast genetic differences between B6J and D2 mice make it difficult to identify key underlying neuro-molecular-genetic factors that contribute to their respective drinking profiles. To address these complications, we studied EtOH and sucrose reinforcement in C57BL/6N mice (B6N), a substrain of the original C57BL/6J line, distinguished by only five small nucleotide polymorphisms, that exhibits significantly reduced EtOH consumption. To determine whether taste-aversion to EtOH is a primary determinant of low EtOH consumption by B6N mice, we subjected animals to a modified sucrose fade procedure using a drinking in the dark, two-bottle-choice paradigm. We determined that; 1) B6Ns consume the same amount of a 10% sucrose solution as B6Js, 2) B6Js consume significantly more of a 10% EtOH/10% sucrose mix than B6Ns, but both achieve physiologically relevant blood alcohol concentrations (15-219 mg%), and 3) B6Js consume significantly more 10% EtOH than B6Ns upon removal of sucrose. Taken together, these results suggest that genetic differences in neurological response to EtOH contribute to differences in EtOH consumption between genetically similar B6J and B6N mice.