NICOTINE WITHDRAWAL AND DEFICITS IN COGNITIVE FLEXIBILITY: POSSIBLE TIES TO ABERRATIONS IN FRONTOSTRIATAL BDNF SIGNALING

Abstract

Nicotine addiction continues to be a leading cause of preventable death worldwide. Despite the plethora of available treatments for smoking cessation, smoking relapse after attempts to quit remains high. It is possible that impairments in cognitive flexibility and underlying neurochemical circuits in nicotine addicts may foster maladaptive behaviors that affect individuals’ ability to refrain from taking drugs. Here we characterized the effects of spontaneous nicotine withdrawal on cognitive flexibility in mice using an operant strategy set-shifting task. Because frontostriatal circuits are critical for cognitive flexibility and brain-derived neurotrophic factor (BDNF) modulates glutamate plasticity, we also explored the effects of nicotine withdrawal on these neurochemical substrates. Adult male C57BL/6J mice were trained in an operant task that required the animals to switch from using a spatial response-driven strategy to a visual cue-based strategy to achieve rewards. Mice were exp