""""""""Reinforcement enhancing effects of NRT"""""""" Nicotine clearly has primary and secondary reinforcing effects, as nicotine is self-administered and stimuli associated with nicotine (""""""""cues"""""""") can become conditioned reinforcers of responding. Overlooked until recently is non-human research showing that nicotine has a third reinforcing function, that of reinforcement enhancing effects, or increasing reinforcing efficacy of rewards unrelated to nicotine intake. Notably, we recently demonstrated reinforcement enhancing effects, perhaps for the first time in humans, of nicotine intake via tobacco smoking, supporting clinical applicability of these preclinical research findings. Similar effects in both nondependent and dependent smokers and other findings indicated dependence and withdrawal as not necessary for these nicotine effects to occur. Yet, these effects may be specific to only some types of reinforcers, especially positive sensory rewards (visual, auditory, etc.). Also, nicotine'kinetics do not influence its reinforcement enhancing effects in animal models, in contrast to its primary and secondary effects, but reinforcement enhancing effects of rapid versus gradual intake of nicotine per se warrants confirmation in humans. Nicotine via means other than smoking, such as nicotine replacement therapy (NRT), can assess effects of nicotine per se on enhancing reinforcement and determine its clinical predictive value in quitting smokers. NRT also can test if pharmacokinetics influences this reinforcement enhancing effect, via rapid (nasal spray) vs. gradual (patch) nicotine intake. Study 1 will examine influences of nicotine per se (versus placebo) on responding for reinforcers in 60 nondependent and dependent smokers to confirm our results with nicotine via smoking, using our well-validated within-subjects design to increase power. We hypothesize that responding will be greater after NRT (patch or spray) versus placebo, indicating reinforcement enhancing effects of nicotine per se, and we will explore whether these effects differ by type of reward, showing specificity. Study 2 will determine if greater reinforced responding due to NRT early in abstinence predicts days to relapse with NRT in 60 treatment-seeking smokers making a permanent quit attempt. We hypothesize that a greater increase in reinforced responding due to NRT early in cessation will predict longer duration of abstinence. This research is highly significant because demonstrating reinforcement enhancing effects of nicotine per se in humans would have important implications for understanding: an overlooked reinforcing effect of nicotine that may help account for persistence of dependence, some of the efficacy of NRT for aiding smoking cessation, and perhaps potentially similar actions of other therapeutic medications or other drugs of abuse.

Public Health Relevance

Reinforcement enhancing effects of NRT This project will examine whether nicotine per se, via NRT, acts in the same way as nicotine via cigarette smoking to enhance the reinforcing value of rewards unrelated to smoking, verifying that preclinical findings with animal models are also observed clinically in humans. Nicotine administration, via NRT patch (gradual intake) and nasal spray (rapid intake), will first be tested to confirm these reinforcement enhancing effects of nicotine per se, and that they do not depend on nicotine's kinetics. A second study will determine if these effects of nicotine via NRT during early abstinence predict better cessation outcome (days to relapse) with NRT in treatment-seeking smokers.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
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Grossman, Debra
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University of Pittsburgh
Schools of Medicine
United States
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Karelitz, Joshua L; Perkins, Kenneth A (2018) Tobacco smoking may delay habituation of reinforcer effectiveness in humans. Psychopharmacology (Berl) 235:2315-2321
Karelitz, Joshua L; Michael, Valerie C; Perkins, Kenneth A (2017) ANALYSIS OF AGREEMENT BETWEEN EXPIRED-AIR CARBON MONOXIDE MONITORS. J Smok Cessat 12:105-112
Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C (2017) Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence. Exp Clin Psychopharmacol 25:249-254
Perkins, Kenneth A; Karelitz, Joshua L (2016) Potential sex differences in the pattern of sensory reinforcers enhanced by nicotine. Exp Clin Psychopharmacol 24:156-61
Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C (2015) Reinforcement enhancing effects of acute nicotine via electronic cigarettes. Drug Alcohol Depend 153:104-8
Perkins, Kenneth A; Karelitz, Joshua L (2015) Sex differences in acute relief of abstinence-induced withdrawal and negative affect due to nicotine content in cigarettes. Nicotine Tob Res 17:443-8
Perkins, Kenneth A; Karelitz, Joshua L (2014) Sensory reinforcement-enhancing effects of nicotine via smoking. Exp Clin Psychopharmacol 22:511-6