Reduction of nicotine content in tobacco products is a regulatory control strategy intended to decrease smoking dependence, and is hypothesized to produce gradual reductions of nicotine intake. Rats were initially trained to self-administer 0.06 mg/kg/infusion nicotine (Phase 1), which was followed by a threshold procedure to determine nicotine demand via a behavioral economics (BE) paradigm (Phase 2). Rats then either self-administered the training dose (high dose group), or were switched to a low dose of nicotine (0.001 mg/kg/infusion; low dose group) in Phase 3. Both groups then underwent a second threshold procedure and demand curves were re-determined (Phase 4). In Phase 5, responding for nicotine was extinguished over the course of 21 sessions. Cue-induced reinstatement was then evaluated (Phase 6). Rats in the low dose group maintained a steady amount of infusions, and thus, did not compensate for nicotine reduction. Rats in the low dose group also showed similar demand elasticity and nicotine seeking (Phase 6) compared to the high dose group, indicating that nicotine reduction did not decrease nicotine demand or seeking. Further, both groups displayed resistance to extinction, indicating that nicotine reduction did not facilitate extinction learning. These results suggest that although compensation of intake does not occur, decreasing the dose of nicotine does not alter nicotine reinforcement value or relapse vulnerability. Further, these results indicate persistence of nicotine-motivated behavior after self-administration of a low nicotine dose. Translationally, these results suggest that alternative strategies may be needed to achieve positive smoking cessation outcomes.

To assess the abuse liability of the JUUL System (JS) in 5.0 % (59 mg/mL) and 3.0 % (35 mg/mL) nicotine concentrations.

While cigarette smoking rates have been steadily decreasing over the past decade, there has been a dramatic increase in nicotine use via e-cigarettes, especially during adolescence. Adolescent e-cigarette use is associated with a greater risk of future cigarette smoking, and increased rates of cigarette smoking in individuals who may have otherwise never tried cigarettes. In humans and rodents, early initiation of nicotine use has been associated with greater consumption, dependence, and persistent nicotine use. The present study sought to investigate the long-lasting effect of daily high-dose nicotine exposure during adolescence on nicotine consumption in adulthood.

Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement.

Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids. The primary objective of this study was to assess the generality of our prior ICSS findings to two additional EC liquids. We also compared effects of "nicotine-free" varieties of these EC liquids on ICSS, as well as binding affinity and/or functional activity of nicotine alone, nicotine-containing EC liquids, and "nicotine-free" EC liquids at nicotinic acetylcholine receptors (nAChRs).

As alcohol and nicotine use disorders are entwined, it may be possible to develop a single medication to treat both. We previously developed a model for ethanol (EtOH) and nicotine co-use in female selectively bred alcohol-preferring (P) rats. To model co-use in a genetically diverse population, we adapted the model to outbred Sprague-Dawley rats of both sexes and assessed the effect of drug pretreatments.

The abuse liability of the JUUL System (JS) in four flavors were evaluated compared to combustible cigarettes, nicotine gum, and a comparator electronic nicotine delivery system (ENDS) with pharmacokinetics (PK) and subjective effects.

The nicotine metabolite ratio (NMR) as measured by the ratio of 3'hydroxycotinine to cotinine has been examined in relation to tobacco use patterns including cigarettes per day and quit success to determine its role in nicotine dependence. We examined the NMR in relation to smoking topography and tested the hypothesis that normal metabolizers have a greater total daily puff volume than slow metabolizers.

There is high comorbidity between antisocial behaviour (ASB) and substance use, and twin studies have shown that part of the covariation is due to overlapping genetic influences. Here we used measured genetic effects to estimate the genetic correlations of ASB with nicotine, alcohol, and cannabis use.

Nicotine vaping and cannabis use are common among youth. Among youth who use e-cigarettes, little is known about how and why they use cannabis and patterns of cannabis and nicotine co-use. Given the popularity of both products among youth, the study aim is to utilize qualitative data to better understand cannabis use among youth who use e-cigarettes.

Use of electronic cigarettes (e-cigarettes) has increased exponentially since their appearance on the U.S. market around 2007. To provide preclinical models of vaping that incorporate olfactory cues and chemosensory effects (including flavors) that play a role in human vaping behavior, the feasibility of using a modified e-cigarette device for delivery of aerosolized nicotine was examined in a nicotine discrimination procedure in mice.

Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes.

Parental smoking and early-emerging nicotine dependence symptoms are well-documented risk factors for adolescent smoking. However, very little is known about the mediating pathways through which these risk factors may act, or whether parental smoking may cause or signal early-emerging nicotine dependence symptoms.

Maternal smoking during pregnancy is correlated with increased substance use in offspring. Research using rodent models shows that gestational nicotine exposure produces enduring alterations in the neurodevelopment of motivational systems, and that rats prenatally treated with nicotine have altered motivation for drug reinforcement on fixed-ratio (FR) schedules of reinforcement.

Electronic nicotine delivery systems (ENDS) differ from combustible cigarettes given that nicotine-salt or nicotine-freebase may be used depending on the product. We have investigated how nicotine-salt and freebase formulations alter e-Vape® self-administration (EVSA) behavior and plasma cotinine levels in male and female mice.

Establishing preclinical models of the development of nicotine withdrawal following acute nicotine exposure could inform tobacco addiction-related research, treatment, and policy. To this end, this lab has previously reported that rats exhibit withdrawal-like elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) following acute nicotine exposure. The goal of this study was to provide further pharmacological characterization of ICSS as a measure of spontaneous and antagonist-precipitated withdrawal from acute nicotine.

To investigate the role of consumption phenotypes as genetic proxies for alcohol misuse and nicotine dependence.

Craving is a major contributor to drug-seeking and relapse. Although the ventral striatum (VS) is a primary neural correlate of craving, strategies aimed at manipulating VS function have not resulted in efficacious treatments. This incongruity may be because the VS does not influence craving in isolation. Instead, craving is likely mediated by communication between the VS and other neural substrates. Thus, we examined how striatal functional connectivity (FC) with key nodes of networks involved in addiction affects relief of craving, which is an important step in identifying viable treatment targets.

The Food and Drug Administration (FDA) is considering setting a nicotine standard for tobacco products to reduce their addictiveness. Such a standard should account for the apparent greater vulnerability to nicotine addiction in some subpopulations, such as adolescents with depression. The present study examined whether the reinforcement threshold and elasticity of demand (i.e., reinforcing efficacy) for nicotine in a genetic inbred rat model of depression (Flinders Sensitive Line [FSL]) differs from an outbred control strain.

Given numerous reports implicating involvement of the precuneus in cue-reactivity paradigms, the goal of this investigation was to examine the relationship between activation of the precuneus in response to drug cues and measures of subjective craving and severity of dependence in volunteers who were comorbid for alcohol and nicotine abuse.