The effects of acute, chronic, and withdrawal from chronic nicotine on novel and spatial object recognition in male C57BL/6J mice

Rationale: Spatial and novel object recognition learning is different from learning that uses aversive or appetitive stimuli to shape acquisition because no overt contingencies are needed. While this type of learning occurs on a daily basis, little is known about how nicotine administration affects it. Objectives: To determine the effects of acute, chronic, and withdrawal from chronic nicotine on two related but distinct incidental learning tasks, novel and spatial object recognition. Methods In C57BL/6J mice, the effects of acute (0.045-0.18 mg/kg), chronic (6.3 mg/kg/day), and withdrawal from chronic nicotine on novel and spatial object recognition were examined. Results: With a 48-h delay between training and testing, acute nicotine enhanced spatial (difference score, saline=3.34 s, nicotine=7.71 s, p=0.029) but resulted in a deficit in novel object recognition (difference score, saline=8.76 s, nicotine= 4.48 s, p=0.033). Chronic nicotine resulted in a strong trend towards a deficit in spatial object recognition (difference score, saline=4.01 s, nicotine=1.81 s, p=0.059) but had no effect on novel object recognition, and withdrawal from chronic nicotine disrupted spatial object recognition (difference score, saline=3.00 s, nicotine=0.17 s, p=0.004) but had no effect on novel object recognition. Conclusions: The effects of nicotine on spatial object recognition shift from enhancement to deficit as administration changes from acute to chronic and withdrawal. These effects were specific for spatial object recognition, which may be due to differing underlying neural substrates involved in these tasks. Understanding how nicotine alters learning has implications for understanding diseases associated with altered cholinergic function.