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

Abstract

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. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Figure 1.

Nicotine-appropriate responding (as a percentage of all) due to intermittent nicotine doses during quantitative testing (top) in: rodents (n=8) trained to discriminate 0 vs 200 μg/kg s.c. (A), and human smokers (n=18) trained to discriminate 0 vs 12 μg/kg via nasal spray (B). Also shown is absolute proportion of the human smokers identifying the spray letter code consistent with nicotine in quantal testing (C). Horizontal lines show 50% of nicotine-appropriate responding, or 50% of participants. Adapted from part of Figure 2 in Chance, et al. (1977), and from Figure 1 in Perkins, DiMarco, et al. (1994). With kind permission from Springer Nature.

Figure 2.

Means (and SEM) for self-reported Acute Cigarette Perceptions (ACP) composite ratings (A, C) and for choice (B, D) of each participant’s discrimination subthreshold nicotine and threshold nicotine cigarettes, each compared to the 0.4 mg/g VLNC, for dependent smokers (top, n=42) and for non-dependent smokers (bottom, n=7). (*** p<.001). Partly adapted from Figures 2 and 3 in Perkins (2019). With kind permission from Oxford University Press.

Figure 3.

Mean ACP difference (A) and mean (+ 95% C.I.) number of puff choices (B) from each higher nicotine content cigarette, vs. the 0.4 mg/g VLNC. Choices are out of a fixed total of 16 per paired cigarette comparison. Horizontal dashed line at 8.0 indicates no difference in choice from the 0.4 mg/g VLNC (i.e., 50% of 16). Non-overlapping 95% C.I. with 8.0 indicates significantly greater choice for that content vs. VLNC. In both graphs, horizontal brackets indicate significant differences between 18.7 mg/g vs. the lower nicotine content cigarettes in ACP or choice. (***p < .001, *p < .05). Partly adapted from Figure 1 in Perkins & Karelitz (2020b). With kind permission from Springer Nature.