The possible impact of menstrual phase upon reactivity to nicotine was investigated in 12 healthy women smokers. Controlled doses of nicotine were administered via an intranasal aerosol delivery ...device to overnight-deprived women smokers in four hormonally verified menstrual phases. Physiological, biochemical, and subjective measures were collected. Cycle-related symptomatology differed significantly across phase, with lowest values during the mid-follicular phase. No significant differences were found for baseline variables, including withdrawal measures. Nicotine increment was stable across phase, confirming reliability of the dosing method. No significant menstrual phase differences were found for physiological, subjective, or biochemical responses to nicotine. Pending investigations conducted over longer intervals, in a wider variety of subjects, findings suggest that for this type of study, complex strategies to control for menstrual-cycle phase effects may be unnecessary.
The effects of nicotine, like those of other drugs with potential for abuse and dependence, are centrally mediated. The impact of nicotine on the central nervous system is neuroregulatory in nature, ...affecting biochemical and physiological functions in a manner that reinforces drug-taking behavior. Dose-dependent neurotransmitter and neuroendocrine effects occur as plasma nicotine levels rise when a cigarette is smoked. Circulating levels of norepinephrine and epinephrine increase, and the bioavailability of dopamine is altered as well. Among the neuroendocrine effects are release of arginine vasopressin, beta-endorphin, adrenocorticotropic hormone, and cortisol. Notably, several of these neurochemicals are psychoactive and/or known to modulate behavior. Thus, affective states or cognitive demands may be favorably modified (at least temporarily) by nicotine intake. When nicotine is inhaled, the neuroregulatory effects just described are immediately available and the reinforcing effects of the drug are maximized. On the other hand, nicotine gum and most other nicotine replacement vehicles in current use have a slower onset of action, resulting in less reinforcement value. Recent data suggest that smoking cessation rates may be optimized by tailoring the dose of nicotine replacement (for example, 2 or 5 mg of nicotine gum) to the individual degree of nicotine dependence. In view of the dynamic interactions between the neuroregulatory effects of nicotine and a host of environmental conditions, nicotine replacement therapy is best carried out in combination with behavior modification techniques.
The emergence of depression early in a quit attempt and its relationship to ability to maintain abstinence were studied in 99 depressed and non-depressed women smokers. Participants rated withdrawal ...symptomatology during a baseline week and the first two weeks of a quit attempt, during which they used a 21-mg nicotine patch and received behavioral counseling. Depressed women experienced greater difficulty maintaining early abstinence than non-depressed women. They were significantly more likely to smoke on the first day of abstinence and smoked marginally more days during the first week. Among participants who relapsed during the first two weeks, latency to relapse was significantly shorter for depressed women. Although craving and all withdrawal symptoms except insomnia showed significant increases over baseline, only depression showed significant group differences, with trend analyses suggesting that depression asymptotes in non-depressed women after the first week but continues increasing in depressed women. Larger increases in depression on the first day of abstinence were associated with earlier lapse. Because depression is relatively infrequent as a withdrawal symptom, it may not be a "true" withdrawal symptom except in depressed people. Identification of depressed smokers and anticipation of their increased need for support during this period may help to counteract the "first-day effect" and difficulties during early abstinence.
The purpose of the present study was to investigate smoking abstinence effects and the dissipation of tolerance (reactivity to nicotine) under controlled laboratory conditions. Seventeen male and ...female regular smokers were tested first in a session following ad libitum smoking and then in an additional five sessions over the course of 11 days during which they abstained from smoking. A metered dose of nicotine was administered via intranasal spray to ensure standard exposure, and pre- and post-dosing measures of heart rate, blood pressure, cortisol, galvanic skin response (GSR), craving, and several DSM-IV withdrawal symptoms (anxiety, irritability, restlessness, difficulty concentrating, and appetite) were collected. Prior to the nicotine test dose during deprivation sessions, heart rate and systolic blood pressure evinced elements of both an 'offset abstinence pattern' (deflection in a direction opposite to that produced by smoking) and a 'transient abstinence pattern' (deflection followed by a subsequent return); for cortisol, an offset pattern was observed, whereas for GSR and craving, a transient pattern was found. With respect to loss of tolerance, heart rate reactivity was found to increase significantly after 2 days' abstinence from nicotine, and the increase was sustained in subsequent sessions. Cortisol reactivity revealed more gradual dissipation, with significant differences evident only after 9 days of abstinence. These findings extend research on nicotine abstinence effects and on the dissipation of tolerance to nicotine deprivation intervals of nearly 2 weeks and confirm prior observations of variability across different response systems.
Both menstrual phase and nicotine have been shown to affect task performance. Though conflicting results have been reported, at least one well-controlled study has demonstrated that women at ...midluteal phase show superior performance on speech articulation and speeded motor coordination tests, but poorer performance on perceptual-spatial tests, than during menses. Smokers have demonstrated superior performance on numerous tasks following nicotine than following placebo. To explore the separate and combined influence of these factors, we studied 13 regularly-menstruating smokers using a two (smoking vs. 12 hours' abstinence) by two (menstrual vs. midluteal phase) factorial design. During each session, subjects completed a test battery including two speeded motor coordination tasks, a computerized reaction time test, and the Stroop (1935) color/word test. Subjects completed the Stroop color and color-word tasks significantly faster after ad lib smoking than after overnight abstinence. No other significant differences emerged. Our findings replicate, in an all-female sample, previous reports that speed of cognitive processing is reduced by nicotine abstinence (or enhanced by nicotine administration). Our failure to observe menstrual cycle effects raises the possibility that the anti-estrogenic effects of smoking may attenuate phase differences in performance.
Recent evidence suggests that cigarette smoking has a heritability index around 53%. While related research on underlying mechanisms also supports the idea that genetic factors contribute to nicotine ...dependence--as well as to cofactors such as substance use and mood disorders--the nature of the behavioral traits and biological capacity for reinforcement that constitutes vulnerability to nicotine dependence is not well understood. The present review explores the problem of why some people become highly nicotine dependent, others develop a pattern of occasional use, and still others avoid the drug entirely despite extensive exposure and widespread experimentation with tobacco in the population. Recent research--both infrahuman and human--suggests that vulnerability to nicotine dependence is related to high initial sensitivity to nicotine and that the development of tolerance is more rapid and self-administration more extensive in such individuals. Relevant findings from neuroscience and biobehavioral research are reviewed in order to identify variables and methodologies that might improve the reliability and validity of behavioral and molecular genetic studies on cigarette smoking. The integration of research in these areas may lead to new insights in the understanding of nicotine dependence as well as to improved techniques for prevention and treatment.
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