Articles
Nicotine Discrimination in Men and Women

https://doi.org/10.1016/S0091-3057(99)00085-4Get rights and content

Abstract

Nicotine is the primary compound that maintains tobacco smoking behavior, and nicotine reinforcement may be related to its discriminative stimulus effects. Nicotine in novel form, isolated from tobacco smoke, is often reinforcing in men but not in women, and clinical trials with nicotine replacement via gum or patch have often shown less efficacy in women vs. men trying to quit smoking. We hypothesize that this sex difference in nicotine reinforcement or clinical efficacy may be related to reduced intensity of nicotine's discriminative stimulus effects in women. Using formal drug discrimination procedures, we have found in several studies that discrimination responding across nasal spray nicotine doses tends to be flatter for women than men (i.e., sex × dose interaction), suggesting reduced sensitivity to changes in dose. Results from the field of psychophysiology, involving detection of physiological changes, are generally consistent with our findings, and suggest that the environmental context accompanying physiological change is important in understanding this sex difference. The implications of this sex difference for smoking cessation treatment and future research directions are presented.

Section snippets

Nicotine dosing and drug discrimination procedures

We have conducted a number of studies examining nicotine discrimination in men and women. To examine individual differences in the magnitude of drug response, it is essential that the drug dose be controlled (9). However, controlling the nicotine dose is difficult when administered by its usual method, tobacco smoking, because of a wide variability in puffing behavior (23). There are also several thousand other compounds in tobacco smoke, so the independent stimulus effects of nicotine as

Sex differences in nicotine discrimination

In several studies of nicotine discrimination, we have observed differential sensitivity of discrimination responding across generalization doses between men and women. In an early study not involving formal drug discrimination training, we gave male and female smokers a different dose of nicotine by nasal spray (0, 5, 10, or 20 μg/kg, in counterbalanced order) on 4 separate days [see (9)]. They were asked to place a check mark next to “nicotine” or “no nicotine” on a form, depending on whether

Nonnicotine effects of smoking

Nevertheless, these results lead to an obvious question: if nicotine is less reinforcing in women, then why is the prevalence of smoking in the U.S. currently about the same for women and men? Because women smoke about as much as men, they must find something else about smoking, besides nicotine, more rewarding than do men. Although nicotine is the primary constituent of tobacco that reinforces smoking behavior, there is evidence that other, sensory, aspects of smoking may also be reinforcing,

Other research consistent with a sex difference in nicotine discrimination

Research from a different field of study, psychophysiology, is also relevant to the discussion of sex differences in nicotine discrimination, and appears to be consistent with our observations (25). There has been significant interest within this field in identifying individual differences in accuracy of perception of physiological changes (which may produce interoceptive stimuli). It is believed that those who are less able to perceive adverse physiological changes (e.g., elevated heart rate),

Conclusions

Several studies have shown that women smokers are less sensitive than men smokers to nicotine's discriminative stimulus effects. Reduced sensitivity to these effects may explain why women appear to find nicotine per se less reinforcing (16), nicotine intake a less reinforcing consequence of tobacco smoking (18), and nicotine replacement less efficacious in reducing withdrawal after cessation (4), relative to men.

Because nicotine replacement is the most common method of treatment for smoking

Acknowledgements

This research was supported by NIDA Grant DA08578. The author thanks Carolyn Fonte, James Grobe, Mark Sanders, Wendy White, and Jacquelyn Ashcom for their helpful assistance.

References (30)

  • W.M. Kallman et al.

    Nicotine as a discriminative stimulus in human subjects

  • J.D. Killen et al.

    Evaluation of a treatment approach combining nicotine gum with self-guided behavioral treatments for smoking relapse prevention

    J. Consult. Clinl. Psychol.

    (1990)
  • K.A. Perkins

    Individual variability in responses to nicotine

    Behav. Genet.

    (1995)
  • K.A. Perkins

    Sex differences in nicotine vs. non-nicotine reinforcement as determinants of tobacco smoking

    Exp. Clin. Psychopharmacol.

    (1996)
  • K.A. Perkins et al.

    Influence of training dose on nicotine discrimination in humans

    Psychopharmacology (Berlin)

    (1996)
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