Pairings of lever and food induce Pavlovian conditioned approach of sign-tracking and goal-tracking in C57BL/6 mice

In rats, Pavlovian sign-tracking has been extensively evaluated as a model of compulsiveness in drug addiction and other addictive behaviors, but it remains unexplored in mice, a species with a wealth of genetically modified models, which makes it possible to examine gene-behavior relationships. In C57BL/6 mice, the most commonly used mouse strain for genetic studies, repeated pairings of lever conditioned stimulus (CS) with food unconditioned stimulus (US) induced Pavlovian conditioning of sign-tracking conditioned response (ST CR) performance of lever CS-directed approach, and Pavlovian conditioning of goal-tracking conditioned response (GT CR) performance of approach responses directed at the location of the food trough where the food US was delivered. The CS–US Paired group performed more ST CRs and more GT CRs during sessions 15–16 than did pseudoconditioning controls which received the lever CS and food US randomly with respect to one another. During sessions 15–16, all mice in the Paired group performed more GT CRs than ST CRs, and regression analysis revealed a positive relationship between an individual subject's tendency to perform ST CRs and GT CRs. The mice that performed more ST CRs during sessions 15–16 yielded higher plasma corticosterone levels. These data reveal stable and reliable acquisition and maintenance of ST CR performance and GT CR performance in mice; however, unlike in rats, ST CRs and GT CRs did not vary inversely within subjects. Corticosterone release, a pathophysiological marker of vulnerability to drug abuse, was positively related to ST CR performance.

► Lever CS–food US pairings induced Pavlovian sign-tracking (ST) and goal-tracking (GT) CR performances in C57BL/6 mice.
► More ST CRs and more GT CRs were performed by subjects receiving CS–US in a Paired procedure than in a Random procedure.
► The mice that exhibited more ST CRs also exhibited more GT CRs.
► The mice that exhibited more ST CRs also exhibited higher corticosterone levels in blood samples taken post-session.