Focal cerebral ischemia impairs motivation in a progressive FR schedule of reinforcement in mice

Abstract Characterization of functional outcome in animal stroke models is essential to improve preclinical drug screenings. Operant procedures showed promising results for the identification of long-lasting functional deficits. In particular, a suppression of lever-pressing in high ratio schedules has been consistently found in rodent models of ischemic stroke. In the present work, we attempted to replicate these isolated observations, by submitting C57Bl/6J mice to a progressive fixed-ratio schedule of reinforcement three weeks after MCAO or sham surgery. Results showed a significant lever-pressing impairment in the MCAO group. Motivational factors (longer post-reinforcement pause, lesser appeal for food rewards) seemed accountable for the deficit, while motor abilities appeared preserved. These findings resemble fatigue-like states experienced by stroke survivors and may be used as long-term measures of behavioral outcome following experimental stroke.