Nicotine

Behavioral Mechanism of Action

The behavioral mechanism of action of nicotine has been related to “mood titration”: the regulation of an individual’s mood by adding known amounts of nicotine over circumscribed periods of time until a given mood state occurs. Nicotine produces both attentional and autonomic arousal, and smoking one or two cigarettes increases resting heart rate by about 5 to 40 beats/min, increases blood pressure 5–20 mmHg, and increases epinephrine and cortisol levels. One representative study found that most smokers report that smoking is pleasurable (81%), helps them concentrate (63%), calms them down when stressed or upset (90%), and helps them deal with difficult situations (82%).

Nicotine paradoxically produces decreases in tension and an anxiolytic-like effect. The basis for such tension reduction is still unknown but may be linked to decreases in skeletal muscle tone, a subsequent reduction of muscle tension, and possibly an analgesic effect. Called Nesbitt’s paradox, smokers allowed to smoke during a stressful experience (for example, in a laboratory setting where they receive painful shocks to the left forearm and upper arm) showed more arousal (an increase in pulse rate) but reported less emotion (more pain endurance and more shocks taken) than smokers who were not allowed to smoke but simulated smoking. These results were interpreted as a paradox, in which smokers exhibit an increase in physiological arousal, but they self-report that they are calmer and more relaxed. A majority of smokers have reported that they smoke to reduce negative mood or to achieve pleasurable relaxation.

Cigarette smokers titrate their level of nicotine intake over the course of a smoking bout, in which the intensity and interval of taking puffs of a single cigarette remain fairly stable and regular while smoking the cigarette. Dependent smokers titrate both their smoking bouts and the number of cigarettes smoked during waking hours. Cigarette smokers will compensate for a reduction of the number of cigarettes smoked by altering the topography of their smoking behavior, with longer and more frequent drags from the cigarette. Low-nicotine cigarettes also lead to similar compensation through increased inhalation and an increase in the number of cigarettes smoked.

Another example of such regulation of nicotine intake is “vent blocking.” To lower the smoke and nicotine content of cigarettes, the filter on the end of a low-yield cigarette is ventilated with holes so that each puff is diluted with ambient air. Smokers unconsciously negate the benefit of this ventilation by blocking the air holes with their lips or fingers. Similar titration can be seen when cigarette smokers are allowed to self-administer nicotine intravenously. When subjects were allowed access to 1.5 mg nicotine per intravenous injection, they all self-administered 18–27 μg/kg, despite wide variations in the number of injections (range, 6–25). The number of injections per session was inversely related to the μg/kg administered. The subjects adjusted their intake to compensate for body mass and presumably the volume of distribution of nicotine in the blood.

The boundary model (for further reading, see Herman and Kozlowski, 1979) explains the mood titration mentioned above. This model proposes three zones of behavioral effects associated with smoking behavior which are delimited by an aversive state of withdrawal when plasma nicotine levels fall below a certain point (the lower boundary) and the noxious aversive state associated with toxic high doses of nicotine (the upper boundary). The zone between the two is called the zone of indifference to nicotine’s pharmacological effects, which can be very large for a nondependent smoker and very small for a heavily dependent smoker (Figure 7.12). A narrow zone of indifference explains the regulation of mood that is hypothesized to be the basis of behavioral mood titration.

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