Nicotine self-administration research: the legacy of Steven R. Goldberg and implications for regulation, health policy, and research

Abstract

Background and rationale

Steven R. Goldberg was a pioneering behavioral pharmacologist whose intravenous drug self-administration studies advanced the understanding of conditioned stimuli and schedules of reinforcement as determinants of pattern and persistence of drug-seeking behavior, and in particular, the importance of nicotine in tobacco use. His passing in 2014 led to invitations to contribute articles to psychopharmacology dedicated to his work.

Objectives

The objectives of this review are to summarize and put into historical perspective Goldberg’s contributions to elucidate the reinforcing effects of nicotine and to summarize the implications of his research for medication development, tobacco regulation, and potential tobacco control policy options. This includes a review of intravenous nicotine self-administration research from the 1960s to 2016.

Results

Goldberg’s application of behavioral pharmacology methods to investigate nicotine reinforcement and the influence of schedule of reinforcement and conditioned stimuli on nicotine administration contributed to the conclusions of the US National Institute on Drug Abuse, and the Surgeon General, that nicotine met the criteria as a dependence-producing drug and cigarette smoking as a prototypic drug dependency or “addiction.” Equally important, this work has been systematically extended to other species and applied to address a range of factors relevant to tobacco use, medication development, regulation, and public health policy.

Conclusions

Steven R. Goldberg was a pioneering scientist whose systematic application of the science of behavioral pharmacology advanced the understanding of tobacco and nicotine use and contributed to the scientific foundation for tobacco product regulation and potential public health tobacco control policy development.

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Notes

  1. 1.

    The FDA guidance document addressing modified risk tobacco products does not advocate for zero or minimal abuse potential of a modified risk tobacco product (MRTP) but requires evidence relevant to its pharmacological abuse liability and attractiveness in behavioral studies of youth, former smokers, and vulnerable populations (FDA 2012). The level of abuse liability that istoo muchfor a MRTP is not defined but will be evaluated by FDA and experts in the MRTP application review process.

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Acknowledgments

The time and effort of Fant, Henningfield, and Kleykamp were supported by PinneyAssociates without input from any such commercial interests. The effort of Donny was supported by the National Institute on Drug Abuse and FDA Center for Tobacco Products (CTP) (U54 DA031659). The effort of Smith was supported by the National Cancer Institute (T32 CA186783). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration. The authors are grateful for the care and efforts of Evan Schnoll and Jonathan Gougelet with editing and referencing.

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Correspondence to Jack E. Henningfield.

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Through Pinney Associates, Drs. Fant, Henningfield, and Kleykamp have consulted or are presently consulting to GlaxoSmithKline on smoking cessation, NJOY on electronic cigarettes, Reynolds American Vapor Products, and to pharmaceutical companies on substance abuse-related regulatory issues on drug products under development. Henningfield shares interest in a patent for a new nicotine gum for smoking cessation that is under license to Niconovum, which is a smoking cessation product subsidiary of Reynolds American, Inc.

Drs. Smith and Donny have no conflicts of interest to report.

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Henningfield, J.E., Smith, T.T., Kleykamp, B.A. et al. Nicotine self-administration research: the legacy of Steven R. Goldberg and implications for regulation, health policy, and research. Psychopharmacology 233, 3829–3848 (2016). https://doi.org/10.1007/s00213-016-4441-4

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Keywords

  • Behavioral pharmacology
  • Self-administration
  • Intravenous
  • Nicotine
  • Tobacco
  • Sensory
  • Second-order schedule
  • Reinforcement
  • Punishment
  • Antagonists