AbstractSprague Dawley (SD) rats are one of the most commonly used outbred rat strains. Despite this, the genetic characteristics of SD are poorly understood. We collected behavioral data from 4,625 SD rats acquired predominantly from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 234,887 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). We also used these data to perform a genome-wide association study (GWAS) of Pavlovian conditioned approach (PavCA), which assesses the propensity for rats to attribute motivational value to discrete, reward-associated cues. Due to the genetic divergence between rats from Charles River and Harlan, we performed two separate GWAS by fitting a linear mixed model that accounted for within vendor population structure and using meta-analysis to jointly analyze the two studies. We identified 18 independent loci that were significantly associated with one or more metrics used to describe PavCA; we also identified 3 loci that were body weight, which was only measured in a subset of the rats. The genetic characterization of SD rats is a valuable resource for the rat community that can be used to inform future study design.Author SummaryOutbred Sprague Dawley rats are among the most commonly used rats for neuroscience, physiology and pharmacological research. SD rats are sold by several commercial vendors, including Charles River Laboratories and Harlan Sprague Dawley Inc. (now Envigo). Despite their wide spread use, little is known about the genetic diversity of SD. We genotyped more than 4,000 SD rats, which we used to characterize genetic differences between SD rats from Charles River Laboratories and Harlan. Our analysis revealed that the two SD colonies are highly divergent. We also performed a genome-wide association study (GWAS) for Pavlovian conditioned approach (PavCA), which assesses the propensity for rats to attribute motivational value to discrete, reward-associated cues. Our results demonstrate that, despite sharing an identical name, SD rats are obtained from different vendors are genetically very different. We conclude that results obtained using SD rats should not be presented without also carefully noting the vendor.
Nicotine-enhanced Pavlovian conditioned approach is resistant to omission of expected outcome