Abstract
The mouse has emerged as a uniquely valuable species for studying the molecular and genetic basis of complex behaviors and modeling neuropsychiatric disease states. While valid and reliable preclinical assays for reward-related behaviors are critical to understanding addiction-related processes, and various behavioral procedures have been developed and characterized in rats and primates, there have been relatively few studies using operant-based addiction-relevant behavioral paradigms in the mouse. Here we describe the performance of the C57BL/6J inbred mouse strain on three major reward-related paradigms, and replicate the same procedures in two other commonly used inbred strains (DBA/2J, BALB/cJ). We examined Pavlovian-instrumental transfer (PIT) by measuring the ability of an auditory cue associated with food reward to promote an instrumental (lever press) response. In a separate experiment, we assessed the acquisition and extinction of a simple stimulus-reward instrumental behavior on a touchscreen-based task. Reinstatement of this behavior was then examined following either continuous exposure to cues (conditioned reinforcers, CRs) associated with reward, brief reward and CR exposure, or brief reward exposure followed by continuous CR exposure. The third paradigm examined sensitivity of an instrumental (lever press) response to devaluation of food reward (a probe for outcome insensitive, habitual behavior) by repeated pairing with malaise. Results showed that C57BL/6J mice displayed robust PIT, as well as clear extinction and reinstatement, but were insensitive to reinforcer devaluation. DBA/2J mice showed good PIT and (rewarded) reinstatement, but were slow to extinguish and did not show reinforcer devaluation or significant CR-reinstatement. BALB/cJ mice also displayed good PIT, extinction and reinstatement, and retained instrumental responding following devaluation, but, unlike the other strains, demonstrated reduced Pavlovian approach behavior (food magazine head entries). Overall, these assays provide robust paradigms for future studies using the mouse to elucidate the neural, molecular and genetic factors underpinning reward-related behaviors relevant to addiction research.
Highlights
The availability of valid and reliable methods for studying incentive learning and other reward-related behaviors in experimental animals is essential to furthering our understanding of the neural, genetic and molecular basis of addiction
Confirming a few previous studies that have reported Pavlovian-instrumental transfer (PIT) in C57BL/6J and C57BL/6J-background mutant mice using comparable procedures as employed here [e.g., 33,34–43], we found robust PIT in this strain
This was evidenced by increased instrumental response rates during presentations of an auditory cue previously associated with reward delivery, compared to presentations of a cue not associated with the reward
Summary
The availability of valid and reliable methods for studying incentive learning and other reward-related behaviors in experimental animals is essential to furthering our understanding of the neural, genetic and molecular basis of addiction. To this end, various rodent behavioral assays have been developed to probe core processes that underlie the natural motivation to seek reward, and that are theorized to go awry in drug abuse and addiction [1,2]. Similar to PIT, both extinction and reinstatement are mediated by the corticolimbic circuits that are persistently altered by drug exposure and implicated in addiction [9,10]
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