Assessment of the inbred C57BL/6 and outbred CD1 mouse strains using a progressive ratio schedule during development

Abstract

Inbred strains have a genetic similarity of at least 98.6% compared to their outbred counterparts. Several studies have shown that inbred C57BL/6 mice and outbred ICR (CD1) mice differ in locomotion, cognitive flexibility, and aggression. However, their performance in operant paradigms is not well understood. A progressive ratio (PR) schedule of reinforcement is a method of quantitative estimation of the incentive state of an animal for a reward by increasing response requirements for reinforcer delivery, which is relevant to assess the breakpoint (amount of response effort an animal is willing to invest for a single unit of reward). This study tested male and female C57BL/6 and CD1 mice with an open field to analyze locomotion. Then, we used conditioning chambers with a PR3 schedule for ten consecutive days (P30-P40). PR performance was measured with the breakpoint, and the mathematical principles of reinforcement (MPR) were used to estimate motivation, impulsivity, and motor skills to manipulate the operandum. We found that CD1 mice showed higher locomotor activity than C57BL/6 independently of sex. CD1 mice had a higher breakpoint. However, male CD1 mice gradually increased breakpoint until the last session. In the MPR model, CD1 mice showed decreased fixed paused parameter (impulsivity) than C57BL/6, independent of sex. Our data suggest that the higher breakpoint in CD1 strain may partially be related to impulsivity. Therefore, the MPR model can help identify factors that affect performances, such as motivation, impulsivity, and motor skills during a PR in adolescent CD1 and C57BL/6 mice. These findings are essential to characterize the differences in the behavioral performance between C57BL/6 and CD1 strains and their potential as animal models.