Operant Sensation Seeking Engages Similar Neural Substrates to Operant Drug Seeking in C57 Mice

Abstract

Novelty and sensation seeking have been associated with elevated drug intake in human and animal studies, suggesting overlap in the circuitry mediating these behaviors. In this study, we found that C57Bl/6J mice readily acquired operant responding for dynamic visual stimuli, a phenomenon we term operant sensation seeking (OSS). Like operant studies using other reinforcers, mice responded on fixed and progressive ratio schedules, were resistant to extinction, and had sustained responding with extended access. We also found that OSS, like psychostimulant self-administration, is sensitive to disruption of dopamine signaling. Low doses of the dopamine antagonist cis-flupenthixol increased active lever responding, an effect reported for psychostimulant self-administration. Additionally, D1-deficient mice failed to acquire OSS, although they readily acquired lever pressing for food. Finally, we found that one common measure of novelty seeking, locomotor activity in a novel open field, did not predict OSS performance. OSS may have predictive validity for screening compounds for use in the treatment of drug addiction. In addition, we also discuss the potential relevance of this animal model to the field of behavioral addictions.