Nicotine as a reinforcer in human subjects and laboratory animals

doi:10.1016/0091-3057(83)90405-7

Pharmacology Biochemistry and Behavior

Volume 19, Issue 6, December 1983, Pages 989-992

https://doi.org/10.1016/0091-3057(83)90405-7 Get rights and content

Abstract

Results are summarized from 17 studies in which intravenous nicotine was evaluated in self-administration paradigms. Six species, ranging from the albino rat to the human, have been tested under a variety of schedules of reinforcement, and as a function of several pharmacologic manipulations. Under certain environmental conditions, it is clear that nicotine can serve as a reinforcer. However, nicotine differs from many other drugs of abuse in that the range of environmental conditions under which it serves as a reinforcer appears to be more restricted.

References (22)

J. Dougherty et al.
Reinforcing and other behavioral effects of nicotine
Neurosci Biobehav Rev
(1981)
R.R. Griffiths et al.
Predicting the abuse liability of drugs with animal drug self-administration procedures: Psychomotor stimulants and hallucinogens
R.R. Griffiths et al.
Pharmacology of cigarette smoking behavior
Trends Pharm Sci
(1982)
J.E. Henningfield et al.
Cigarette smokers self-administer intravenous nicotine
Pharmacol Biochem Behav
(1983)
W.J. Lang et al.
Self-administration of nicotine with and without a food delivery schedule
Pharmacol Biochem Behav
(1977)
A.A. Latiff et al.
Effects of changing dosage and urinary pH in rats self-administering nicotine on a food delivery schedule
Pharmacol Biochem Behav
(1980)
G. Singer et al.
Schedule induced self injections of nicotine with recovered body weight
Pharmacol Biochem Behav
(1978)
G. Singer et al.
Effects of dopaminergic nucleus accumbens lesions on the acquisition of schedule induced self injection of nicotine in the rat
Pharmacol Biochem Behav
(1982)
L.A. Smith et al.
Changes occurring in self administration of nicotine by rats over a 28-day period
Pharmacol Biochem Behav
(1980)
N.A. Ator et al.
Intravenous self-administration of nicotine in the baboon

G.A. Deneau et al.

Nicotine self-administration in monkeys

Ann NY Acad Sci

(1967)

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Nicotine has a unique profile among drugs of abuse. To the noninitiated user, nicotine has powerful aversive effects and its relatively weak euphorigenic effects undergo rapid tolerance. Despite this, nicotine is commonly abused despite negative heath consequences, and nicotine users have enormous difficulty quitting. Further, nicotine is one of the most commonly co-abused substances, in that it is often taken in combination with other drugs. One explanation of this polydrug use is that nicotine has multiple appetitive and consummatory conditioning effects. For example, nicotine is a reinforcement enhancer in that it can potently increase the incentive value of other stimuli, including those surrounding drugs of abuse such as alcohol. In addition, nicotine also has a unique profile of neurobiological effects that alter regulation of alcohol intake and interoception. This review discusses the psychological and biological mechanisms surrounding nicotine's appetitive conditioning and consummatory effects, particularly its interactions with alcohol.
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Citation Excerpt :
Tobacco smoking typically begins in adolescence, initially through experimentation and is determined by multiple factors including the influence of family members, peers, culture and genetics (Mayhew et al. 2000). Nicotine is the primary psychoactive ingredient in tobacco and studies in humans and in animals have shown that it is a powerful reinforcer, leading to the dominant view that nicotine is a primary ingredient in tobacco that contributes to its addictive property (Henningfield and Goldberg, 1983; Stolerman and Jarvis 1995). There is considerable understanding in the direct interaction between nicotine and the regulation of central reward systems that likely drive nicotine reinforcement (see Section 2.2).
Nicotine use and dependence, typically achieved through cigarette smoking, but increasingly through vape products, is the leading cause of preventable death today. Despite a recognition that many current smokers would like to quit, the success rate at doing so is low and indicative of the persistent nature of nicotine dependence and the high urge to relapse. There are currently three main forms of pharmacotherapy approved as aids to treat nicotine dependence: a variety of nicotine replacement products (NRT's), the mixed NA/DA reuptake inhibitor bupropion (Zyban®), and the preferential nicotinic α4β2 receptor agonist drug, varenicline (Chantix®); the latter being generally recognized to be the most effective. However, each of these approaches afford only limited efficacy, and various other pharmacological approaches are being explored. This chapter focusses on approaches targeted to the serotonin (5-HT) system, namely, selective serotonin reuptake inhibitors (SSRI's) which served a pioneer role in the investigation of serotoninergic modulators in human smoking cessation trials; and secondly drugs selectively interacting with the 5-HT2A and 5-HT2C receptor systems. From an efficacy perspective, measured as smoking abstinence, the 5-HT2A agonist psychedelics, namely psilocybin, seem to show the most promise; although as the article highlights, these findings are both preliminary and there are significant challenges to the route to approval, and therapeutic use of this class should they reach approval status. Additional avenues include 5-HT2C receptor agonists, which until recently was pioneered by lorcaserin, and 5-HT2A receptor antagonists represented by pimavanserin. Each of these approaches has distinct profiles across preclinical tests of nicotine dependence, and may have therapeutic potential. It is anticipated as diagnostic and predictive biomarkers emerge, they may provide opportunities for subject stratification and opportunities for personalizing smoking cessation treatment. The clinical assessment of SSRI, 5-HT2A and/or 5-HT2C receptor-based treatments may be best served by this process.
Clinical laboratory studies of smokeless tobacco use
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Nicotine is the primary addictive constituent of tobacco products. The purpose of the chapter is to review the findings of clinical smokeless tobacco (ST) laboratory studies of use characteristics, user preferences, and additive content. Assessment tools such as the Fagerström Test for Nicotine Dependence-Smokeless Tobacco (FTND-ST), the Hooked on Nicotine Checklist (HONC), and the Product Evaluation Scale (PES) are discussed and their strengths and limitations noted. The absorption of nicotine from ST products is contingent upon both user behaviors and product characteristics. Particular emphasis is placed on characteristics that affect nicotine bioavailability and thus addiction liability. Some other factors that affect use, such as format, are mentioned. Projections and suggestions are offered for the future of clinical laboratory studies.
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The evolution of science derives, in part, from the development and use of new methods and techniques. Here, we discuss one development that may have impact on the understanding of tobacco regulatory science: namely, the application of behavioral economics to the complex tobacco marketplace. The purpose of this paper is to review studies that examine conditions impacting the degree to which electronic nicotine delivery system (ENDS) products substitute for conventional cigarettes in the Experimental Tobacco Marketplace (ETM). Collectively, the following factors constitute the current experimental understanding of conditions that will affect ENDS use and substitution for conventional cigarettes: increasing the base price of conventional cigarettes, increasing taxation of conventional cigarettes, subsidizing the price of ENDS products, increasing ENDS nicotine strength, and providing narratives that illustrate the potential health benefits of ENDS consumption in lieu of conventional cigarettes. Each of these factors are likely moderated by consumer characteristics, which include prior ENDS use, ENDS use risk perception, and gender. Overall, the ETM provides a unique method to explore and identify the conditions by which various nicotine products may interact with one another that mimics the real world. In addition, the ETM permits the efficacy of a broad range of potential nicotine policies and regulations to be measured prior to governmental implementation.

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Nicotine as a reinforcer in human subjects and laboratory animals

Abstract

Neurosci Biobehav Rev

Trends Pharm Sci

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Intravenous self-administration of nicotine in the baboon

Nicotine self-administration in monkeys

Ann NY Acad Sci