Status and future directions of preclinical behavioral pharmacology in tobacco regulatory science.

Abstract

Behavioral pharmacology is a branch of the experimental analysis of behavior that has had great influence in drug addiction research and policy. This paper provides an overview of recent behavioral pharmacology research in the field of tobacco regulatory science, which provides the scientific foundation for the Food and Drug Administration Center for Tobacco Products (FDA CTP) to set tobacco control policies. The rationale and aims of tobacco regulatory science are provided, including the types of preclinical operant behavioral models it deems important for assessing the abuse liability of tobacco products and their constituents. We then review literature relevant to key regulatory actions being considered by the FDA CTP, including regulations over nicotine and menthol content of cigarettes, and conclude with suggesting some directions for future research. The current era of tobacco regulatory science provides great opportunities for behavioral pharmacologists to address the leading cause of preventable death and disease worldwide.

Cigarette Smoke Extract, but Not Electronic Cigarette Aerosol Extract, Inhibits Monoamine Oxidase in vitro and Produces Greater Acute Aversive/Anhedonic Effects Than Nicotine Alone on Intracranial Self-Stimulation in Rats

“…), cigarette smoke (CS) contains considerably higher levels of several behaviorally active non-nicotine constituents including monoamine oxidase (MAO) inhibitors (e.g., the β-carbolines harmane and norharmane, also called harman and norharman), minor tobacco alkaloids (e.g., nornicotine, anabasine), and volatile organic compounds (VOCs) (e.g., acetaldehyde, toluene) (e.g., Margham et al, 2016 ; National Academies of Sciences, Engineering, and Medicine, 2018 ; Belushkin et al, 2020 ). These compounds can mimic or enhance nicotine’s addiction-related effects in preclinical models, or may have abuse liability themselves (for review, see Hoffman and Evans, 2013 ; LeSage et al, 2018 ). The greater abuse liability of cigarettes versus ANDs may therefore reflect the higher levels of MAO inhibitors and other behaviorally active non-nicotine constituents in CS.…”

Multifactorial Etiology of Adolescent Nicotine Addiction: A Review of the Neurobiology of Nicotine Addiction and Its Implications for Smoking Cessation Pharmacotherapy

“…Preclinical models and human studies have demonstrated that nicotine has cognitive-enhancing effects and these effects of nicotine may be an important factor in vulnerability to Tobacco Use Disorder (TUD) and may also contribute to difficulty in quitting smoking. The positive reinforcement effects of nicotine reflect nicotine's inherently rewarding effects that increase the probability of continued self-administration, and for both, the initiation and maintenance of tobacco use (1)(2)(3). Preclinical models typically used cell cultures or animal models that involve administration of nicotine to rodents.…”

β-Carbolines found in cigarette smoke elevate intracranial self-stimulation thresholds in rats

“…Nicotine is the primary addictive constituent in tobacco products, but other tobacco constituents may also contribute to tobacco use (e.g., Brennan et al, 2014;Hoffman and Evans, 2013;LeSage et al, 2018). For example, cigarette smoke contains various compounds (e.g., β-carbolines, 2-naphthylamine) that inhibit monoamine oxidase (MAO), an enzyme that degrades monoamines (e.g., dopamine, serotonin), and both isozymes of MAO (MAO-A and MAO-B) are inhibited in smokers (Fowler et al, 1996a;Fowler et al, 1996b;Hogg, 2016).…”