Gradual and Immediate Nicotine Reduction Result in Similar Low-Dose Nicotine Self-Administration

Smith, Tracy T.; Levin, Melissa; Schassburger, Rachel L.; Buffalari, Deanne M.; Sved, Alan F.; Donny, Eric C.

doi:10.1093/ntr/ntt082

Cited by 26 publications

(47 citation statements)

References 22 publications

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“…Standard self-administration operant chambers (ENV-008 CT; Med-Associates) were configured as previously described (Smith et al, 2013), and included two nosepoke holes below two stimulus lights on one side of the chamber. For self-administration experiments, the houselight was lit red during the session, and in the experiment on reinforcement enhancement the houselight was lit white during the session and turned off as part of the VS reinforcer (details below).…”

Section: Apparatusmentioning

confidence: 99%

“…Procedures for jugular catheterization were as previously described (Smith et al, 2013). For the first 5 days following surgery, rats had their catheter flushed once-daily with 0.1 ml of a sterile saline solution containing heparin (3 U), an antibiotic, and streptokinase (833.3 U) to maintain catheter patency and prevent infection.…”

Section: Procedures For Self-administration Experimentsmentioning

confidence: 99%

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Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine

Smith

Rupprecht

Cwalina

et al. 2016

Neuropsychopharmacol

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The Food and Drug Administration (FDA) has the authority to regulate cigarette smoke constituents, and a reduction in nicotine content might benefit public health by reducing the prevalence of smoking. Research suggests that cigarette smoke constituents that inhibit monoamine oxidase (MAO) may increase the reinforcing value of low doses of nicotine. The aim of the present experiments was to further characterize the impact of MAO inhibition on the primary reinforcing and reinforcement enhancing effects of nicotine in rats. In a series of experiments, rats responded for intravenous nicotine infusions or a moderately-reinforcing visual stimulus in daily 1-h sessions. Rats received pre-session injections of known MAO inhibitors. The results show that (1) tranylcypromine (TCP), a known MAO inhibitor, increases sensitivity to the primary reinforcing effects of nicotine, shifting the dose-response curve for nicotine to the left, (2) inhibition of MAO-A, but not MAO-B, increases low-dose nicotine self-administration, (3) partial MAO-A inhibition, to the degree observed in chronic cigarette smokers, also increases low-dose nicotine self-administration, and (4) TCP decreases the threshold nicotine dose required for reinforcement enhancement. The results of the present experiments suggest cigarette smoke constituents that inhibit MAO-A, in the range seen in chronic smokers, are likely to increase the primary reinforcing and reinforcement enhancing effects of low doses of nicotine. If the FDA reduces the nicotine content of cigarettes, then variability in constituents that inhibit MAO-A could impact smoking.

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Section: Apparatusmentioning

confidence: 99%

Section: Procedures For Self-administration Experimentsmentioning

confidence: 99%

Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine

Smith

Rupprecht

Cwalina

et al. 2016

Neuropsychopharmacol

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“…Procedures for jugular catheterization were as previously described (Smith et al 2013). Rats were allowed at least five days of recovery following surgery.…”

Section: Methodsmentioning

confidence: 99%

“…Standard self-administration experimental chambers (ENV-008 CT; Med-Associates) were configured as previously described (Smith et al 2013), and included two nose poke holes below two stimulus lights on one wall of the chamber. Rats were given the opportunity to respond via nosepokes for i.v.…”

Section: Methodsmentioning

confidence: 99%

“…The other six combinations all required the same number of responses to earn an infusion, but the dose of nicotine decreased across unit prices (i.e., dose reduction). Nicotine doses in this experiment were chosen to be in a range expected to maintain self-administration behavior (Smith et al 2013). Rats experienced four sessions at each unit-price combination, and each rat experienced the combinations in a random order.…”

Section: Methodsmentioning

confidence: 99%

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Characterizing the relationship between increases in the cost of nicotine and decreases in nicotine content in adult male rats: implications for tobacco regulation

et al. 2016

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BACKGROUND A large reduction in the nicotine content of cigarettes may benefit public health by reducing the rate and the prevalence of smoking. A behavioral economics framework suggests that a decrease in nicotine content may be considered an increase in the unit price of nicotine (unit price = reinforcer cost / reinforcer magnitude). Increasing the price of cigarettes (i.e., increasing reinforcer cost) would be considered an equivalent change in unit price to reducing nicotine content (i.e., reducing reinforcer magnitude). OBJECTIVES The goal of the present experiments was to characterize the relationship between increases in nicotine cost and decreases in nicotine dose. MATERIALS AND METHODS A rat self-administration model was used to assess this relationship across three experiments, with an emphasis on very low nicotine doses to model a potential nicotine reduction policy. Cost was manipulated via changes in the number of responses required to earn an infusion. RESULTS Results show that increases in the cost of nicotine and decreases in nicotine content were not equivalent manipulations. Nicotine consumption was more sensitive to nicotine dose than to nicotine cost. Nicotine consumption was also not equivalent across a variety of cost and dose combinations forming a single unit price. CONCLUSIONS Results of the present studies suggest that nicotine reduction is likely to have a large impact on nicotine exposure from cigarettes.

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Behavioral Mechanisms Underlying Nicotine Reinforcement

Rupprecht

Smith

Schassburger

et al. 2015

Current Topics in Behavioral Neurosciences

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Cigarette smoking is the leading cause of preventable deaths worldwide and nicotine, the primary psychoactive constituent in tobacco, drives sustained use. The behavioral actions of nicotine are complex and extend well beyond the actions of the drug as a primary reinforcer. Stimuli that are consistently paired with nicotine can, through associative learning, take on reinforcing properties as conditioned stimuli. These conditioned stimuli can then impact the rate and probability of behavior and even function as conditioning reinforcers that maintain behavior in the absence of nicotine. Nicotine can also act as a conditioned stimulus, predicting the delivery of other reinforcers, which may allow nicotine to acquire value as a conditioned reinforcer. These associative effects, establishing non-nicotine stimuli as conditioned stimuli with discriminative stimulus and conditioned reinforcing properties as well as establishing nicotine as a conditioned stimulus, are predicted by basic conditioning principles. However, nicotine can also act non-associatively. Nicotine directly enhances the reinforcing efficacy of other reinforcing stimuli in the environment, an effect that does not require a temporal or predictive relationship between nicotine and either the stimulus or the behavior. Hence, the reinforcing actions of nicotine stem both from the primary reinforcing actions of the drug (and the subsequent associative learning effects) as well as the reinforcement enhancement action of nicotine which is non-associative in nature. Gaining a better understanding of how nicotine impacts behavior will allow for maximally effective tobacco control efforts aimed at reducing the harm associated with tobacco use by reducing and/or treating its addictiveness.

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Gradual and Immediate Nicotine Reduction Result in Similar Low-Dose Nicotine Self-Administration

Cited by 26 publications

References 22 publications

Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine

Effects of Monoamine Oxidase Inhibition on the Reinforcing Properties of Low-Dose Nicotine

Characterizing the relationship between increases in the cost of nicotine and decreases in nicotine content in adult male rats: implications for tobacco regulation

Behavioral Mechanisms Underlying Nicotine Reinforcement

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