Preclinical and clinical research on the discriminative stimulus effects of nicotine

Shoaib, Mohammed; Perkins, Kenneth A.

doi:10.1016/j.neuropharm.2020.108063

Cited by 10 publications

(6 citation statements)

References 118 publications

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“…That change, also labeled the drug’s interoceptive stimuli, allows the individual to discriminate between administered drug conditions, such as active drug from placebo (vehicle), one drug from a different drug, between different doses of the same drug (very relevant in the smoked nicotine section of this review), and so forth. Those interoceptive drug stimuli act as cues to direct behavior, and the pattern of that change in internal state can be used to train individuals to respond in specific ways to provide an objective means of documenting that state has been perceived (Shoaib & Perkins, 2020; Siegel, 1991).…”

Section: Background On Nicotine Discriminationmentioning

confidence: 99%

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

Perkins¹

2022

Experimental and Clinical Psychopharmacology

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This review of research on behavioral discrimination of nicotine and how it informs public health policy for reducing risk of tobacco dependence is adapted from Kenneth A. Perkins’s American Psychological Association Division 28 (Psychopharmacology and Substance Abuse) 2020 Med Associates Brady/Schuster Award Lecture. The author’s initial programmatic clinical research on nicotine is introduced, especially efforts to develop and validate a novel method of acute nicotine dosing. After the public health rationale for characterizing the discriminative stimulus effects of nicotine in humans are described, details from two separate programs of research on nicotine discrimination in humans are presented. The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine’s neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects. The second, more recent program focused on threshold doses for discrimination of nicotine by cigarette smoking, a program that was very difficult to do until the past decade, and how nicotine’s self-reported “reward” and preference via choice behavior relate to its discriminability. Differences due to menthol and degree of tobacco dependence were also examined. For each of these two programs, the main findings of selected studies are noted, followed by very recent work on nicotine discrimination and choice that informs Food and Drug Administration’s efforts to formulate public policy to improve health and reduce the nearly half million American deaths per year due to persistent tobacco use.

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Section: Background On Nicotine Discriminationmentioning

confidence: 99%

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

Perkins¹

2022

Experimental and Clinical Psychopharmacology

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“…The stimulus effects of drugs are pharmacologically selective, dose-dependent, and highly correlated with the abuse-related human subjective effects (Bolin et al, 2016;Perkins et al, 1999). As such, the drug discrimination procedure may be an extremely valuable approach to generating valuable information to help shape data-driven regulatory policy decisions with regard to nicotine delivery devices including ENDS (Shoaib and Perkins;2020).…”

Section: Introductionmentioning

confidence: 99%

Assessment of Abuse-Related Discriminative Stimulus Effects of Nicotine Aerosol in Rodents

Alkhlaif

Shelton

2023

J Pharmacol Exp Ther

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The rapid increase in e-cigarette use highlights the importance of developing relevant, predictive animal models exploring their potential health implications. The goal of the present study was to examine the abuse-related effects of brief, repeated e-cigarette aerosol exposures in rodents modeling human e-cigarette user behavior. We evaluated the discriminative stimulus effects of brief, repeated puffs of inhaled nicotine in rats that had been trained to discriminate injected nicotine from saline. Locomotor activity measurement following exposure to injected and aerosolized nicotine was also assessed as an additional behavioral outcome. We hypothesized that the stimulus effects of nicotine aerosol were CNS mediated and comparable to that produced by an injected nicotine training stimulus. We further hypothesized that number of aerosol puffs and the e-liquid nicotine concentration which was aerosolized would impact the substitution of nicotine aerosol for injected nicotine. Both nicotine injections and exposures to nicotine aerosol produced a dose-dependent effect on locomotor activity. Nicotine aerosol under our puffing conditions produced e-liquid nicotine concentration-dependent and puff-numberdependent complete substitution for the injected nicotine training condition. The nicotinic antagonist, mecamylamine, completely blocked nicotine-appropriate responding produce by the training dose of 0.3 mg/kg injected nicotine as well as that resulting from exposure to aerosol puffs generated by e-liquid containing 3 mg/ml nicotine, demonstrating that the stimulus of inhaled nicotine was most likely CNS-mediated and not due to olfactory stimulus properties.Overall, the results support the hypothesis that an aerosol exposure drug discrimination model in rodents has applicability to studying the abuse-related effects of e-cigarettes.

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“…Consumption of nicotine by humans has perceptible internal (interoceptive) stimulus effects that contribute to its use liability (Perkins 1999; Murray and Bevins 2007a,b; Wooters et al , 2009; Bevins and Besheer 2014; Shoaib and Perkins 2020). The neuropharmacology of these interoceptive stimulus effects of nicotine has been widely studied in rodents using the two-operands (e.g.…”

Section: Introductionmentioning

confidence: 99%

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes

Thompson

Tracy

Huynh

et al. 2022

Behavioural Pharmacology

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Varenicline (Chantix) is an FDA-approved smoking cessation aid that is pharmacologically similar to nicotine, the primary addictive component found within tobacco. In support of this similarity, previous drug discrimination research in rats has reported that the internal or interoceptive stimulus effects of nicotine and varenicline share stimulus elements. Those shared elements appear to be mediated, in part, by overlapping action at alpha4beta2–containing nicotinic acetylcholine receptors (nAChRs). The research supporting this conclusion, however, has only used nicotine, and not varenicline, as the training drug. Accordingly, we used the discriminated goal tracking (DGT) task in which 1 mg/kg varenicline signaled intermittent access to sucrose. On separate intermixed saline days, sucrose was not available. Rats acquired the discrimination as measured by a differential increase in dipper entries (goal tracking) evoked by varenicline. These rats then received a series of tests with several doses of varenicline, nicotine, nornicotine (a metabolite of nicotine and tobacco alkaloid), sazetidine-A (a partial alpha4beta2 agonist), PHA-543613 (an alpha7 agonist), and bupropion (a norepinephrine and dopamine reuptake inhibitor). Control of goal tracking by varenicline was dose-dependent. Nicotine and nornicotine evoked responding comparable to the varenicline training dose indicating full substitution. Sazetidine-A partially substituted for the varenicline stimulus, whereas bupropion and PHA-543613 evoked little to no varenicline-like responding. These findings indicate that varenicline can serve as the training stimulus in the DGT task. Further, stimulus control of varenicline in the DGT task is driven by its partial agonist activity at alpha4beta2–containing nAChRs. The use of this approach could lead to a better understanding of the pharmacological action of varenicline and help guide treatment geared towards tobacco cessation through a more targeted development of novel synthetically designed, subunit-specific pharmacological interventions.

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Preclinical and clinical research on the discriminative stimulus effects of nicotine

Cited by 10 publications

References 118 publications

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

Assessment of Abuse-Related Discriminative Stimulus Effects of Nicotine Aerosol in Rodents

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes

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