Pharmacologic and sensorimotor components of satiation in cigarette smoking

https://doi.org/10.1016/j.pbb.2003.07.002Get rights and content

Abstract

To examine mechanisms underlying satiation in cigarette smoking, 18 smokers received intravenous (iv) nicotine, alone or in combination with denicotinized cigarette smoke. Nicotine was administered using programmed presentations of either pulsed injections or continuous infusions, with iv saline serving as a control. A high-nicotine cigarette smoke condition (usual brand) was also presented. During each of the six test sessions, subjects were allowed to puff on their usual brands of cigarette ad libitum while the programmed satiation conditions were in force. Administration of iv nicotine caused a small suppression of ad libitum smoking behavior; denicotinized smoke produced a significantly larger reduction, showing that short-term satiation is more dependent on the presentation of smoke than delivery of nicotine per se. However, denicotinized smoke alone did not have as much effect as puffs from the usual brands of cigarettes. The combination of iv nicotine and denicotinized smoke puffs produced equivalent satiation to that of the usual brand. Cigarette craving and negative affect were partially relieved by iv nicotine presentations as well as by denicotinized smoke, and again the combination of iv nicotine and denicotinized smoke approximated the effects of the usual brand. The results of this study underscore the importance of both sensorimotor aspects of smoking and the pharmacologic effects of nicotine in tobacco dependence.

Introduction

In designing treatments for smoking reduction or cessation, it may be helpful to identify which aspects of smoking behavior relieve tobacco withdrawal symptoms or produce behavioral satiation, i.e., a short-term suppression in ad libitum smoking following consumption of smoke constituents. Previous studies of tobacco withdrawal have documented the effects of nicotine, administered by a variety of routes, in alleviating withdrawal symptoms Gross and Stitzer, 1989, Hughes et al., 1984, Perkins et al., 1992, Rose et al., 1984. On the other hand, nonnicotine aspects of smoking have also been shown to relieve craving and other smoking withdrawal symptoms, possibly because of the conditioned effects of smoke cues Pickworth et al., 1999, Rose and Levin, 1991.

Other studies have focussed on the role of nicotine in regulating ad libitum smoking behavior, and manipulations of cigarette nicotine delivery have indeed been shown to modulate the rate of smoking. Increasing nicotine delivery tends to reduce smoke intake, and conversely, lowering nicotine delivery tends to increase smoking behavior (McMorrow and Foxx, 1983). The phenomenon of “titration” of nicotine intake is imprecise, however, and smokers only crudely regulate their nicotine levels within wide bounds (Kozlowski and Herman, 1984). Studies of titration, while showing some role for nicotine, leave unanswered the question of what components of cigarette smoke might be sufficient to completely satisfy the desire to engage in further smoking behavior, i.e., induce satiation.

Previous studies in our laboratory have suggested that sensorimotor cues involved in the act of smoking play a significant role in providing satisfaction and modulating smoking behavior. For example, in one study, a low-nicotine smoking condition presenting relatively high intensity sensory cues did not elicit compensatory increases in smoking that were observed with low-sensory, low-nicotine smoke (Rose et al., 1993). In other studies in which the nicotine and sensorimotor components of cigarette smoking were dissociated, using iv nicotine and denicotinized smoke presentations, iv nicotine was rated as much less satisfying than denicotinized cigarette smoke, highlighting the importance of sensorimotor aspects for smoking satisfaction Rose et al., 2000, Westman et al., 1996. However, these studies did not measure how the rate of smoking a preferred brand of cigarette might be affected by different satiation manipulations. This shortcoming posed an interpretational problem because the type of smoke used to provide satiation was the same as that used to measure ad libitum smoking. Thus, a reduction in ad libitum smoking might have reflected not only satiation but a reduction in the palatability of the smoke tested in a given condition. In the current study, the test cigarette used for ad libitum smoking was held constant across conditions, and the relative efficacy of the different satiation manipulations could be ascertained.

We examined the ability of a variety of manipulations to satiate smokers. At one extreme, we presented programmed puffing of the usual brand of cigarette in an amount equal to that which each subject normally smoked in the same length of time (assessed during a baseline session). We expected that this satiation manipulation would nearly completely suppress concurrent ad libitum smoking. At the opposite extreme, subjects received saline infusions without any programmed puffing; the expectation was that ad libitum consumption of their usual-brand cigarettes would be maximal in this condition. Between these extremes, there were four other satiation conditions designed to provide one or another component of smoke and yield information about the efficacy of different smoke components in reducing ad libitum smoking. Three of these conditions presented iv nicotine, administered in puff-sized “bolus” injections or as a continuous infusion, and in one of these conditions, the iv nicotine pulses were accompanied by programmed puffing on a denicotinized cigarette. In a different condition, puffs of a denicotinized cigarette were presented accompanied by saline infusion. We expected partial satiation with presentations of the nicotine alone or with denicotinized smoke alone, but we predicted that the combination of denicotinized smoke with iv nicotine would recapture the full satiating potency of presentations of smoke from the usual-brand cigarettes.

Section snippets

Methods

The research was approved by the Duke University Medical Center Institutional Review Board, and written informed consent was obtained from all participants.

Subject characteristics

Table 2 summarizes the demographic characteristics and smoking habits of the participants in the study.

Compliance with overnight abstinence

Baseline plasma nicotine and CO levels did not differ across conditions, and the values were consistent with overnight abstinence. Mean baseline plasma nicotine concentration was 4 ng/ml (S.D.=2.4) and expired air CO concentrations averaged 12 ppm (S.D.=4.9). The mean baseline cotinine level was 245 ng/ml (S.D.=106.7).

Validation of nicotine and smoke administration procedures

Because only one iv catheter was inserted for each participant, blood

Discussion

The main result of this study was that a considerable degree of satiation, measured by a reduction in ad libitum smoking of the usual-brand cigarettes, was obtained when subjects were provided with the sensorimotor components of smoking, delivered by puffs of denicotinized cigarettes. The finding that denicotinized smoke produced a large satiation effect is consistent with our previous studies and with those from other laboratories showing that sensorimotor cues provide an important component

Acknowledgements

This work was supported by Grant DA 02665 from the National Institute on Drug Abuse.

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