Date of Completion


Embargo Period



Nicotine, Human, Reward, Conditioning, Fear, Anxiety

Major Advisor

Robert Astur

Associate Advisor

John Salamone

Associate Advisor

Thomas Gould

Associate Advisor

Etan Markus

Associate Advisor

Ian Stevenson

Field of Study



Doctor of Philosophy

Open Access

Open Access


Although considerable progress has been made, we do not fully understand the neuropsychological properties of nicotine that drive nicotine dependence. The present body of work provides an original investigation of the effects of nicotine on behavioral and physiological responding for rewarding and aversive stimuli in humans, which arises from considerable nonhuman investigations of nicotine’s complex interactions in conditioned learning. In order to accomplish this goal, three distinct studies were conducted. Given evidence that nicotine enhances operant responding for nonpharmacological reinforcers, Study 1 assessed the ability of nicotine to enhance food reward sensitivity using a virtual reality conditioned place preference paradigm. Acute administration of nicotine prior to conditioning resulted in partial reward enhancement in that nicotine-treated participants demonstrated place preferences by spending significantly more time in the previously rewarded context, while the placebo group did not. However, we did not observe significant differences between treatment groups. Study 2 explored differences in reward responding between nicotine users and non-users. Research suggests that nicotine users assign enhanced motivational salience to nicotine rewards; however, discrepancies exist as to whether this enhanced salience modulates the reward value of non-drug cues. Using physiological measures and explicit pleasurability ratings of affectively rewarding stimuli and drug-related cues, we found that nicotine users attributed enhanced incentive salience to nicotine rewards relative to non-users. However, we found little evidence of hyporeactivity to non-nicotine rewards among nicotine users. We also examined the effects of acute nicotine administration on these measures of reward processing but found no effect of nicotine in our nondependent sample. Finally, to extend nonhuman findings that nicotine particularly facilitates hippocampal-dependent fear learning, Study 3 measured the effects of acute nicotine on conditioned fear using a novel virtual reality fear conditioning paradigm. We observed nicotine-enhanced contextual fear learning but found no enhancement of trace fear. Hypotheses generated by these data provide insight into the mechanisms that underlie nicotine dependence and anxiety disorder comorbidity, as well as risks for the development and maintenance of nicotine use, and risks for relapse following cessation. Ongoing research may aid in the development of behavioral and pharmacological interventions and treatments for nicotine dependence.