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Nicotine intake, menstrual and smoking withdrawal symptomatology, and baseline cortisol and MHPG were assessed in nine women smokers under conditions of ad lib smoking and overnight abstinence in three menstrual phases (early follicular, mid-to-late follicular, and late luteal). A trend towards higher nicotine intake (p < 0.10) was observed in the mid-to-late follicular phase. Although menstrual symptomatology was not significantly elevated during the smoking abstinence condition overall, abstinence appeared to prevent the normal reduction in symptomatology during the mid-to-late follicular phase that occurred under conditions of ad lib smoking. Menstrual and withdrawal symptoms were highly correlated, and both were most pronounced during the late luteal/abstinence condition. The smoking-specific item "craving" reflected this pattern, though in attenuated form, suggesting that the observed exacerbation of withdrawal symptomatology was not simply due to generalized dysphoria, as queried in both instruments. MHPG was significantly elevated in the late luteal phase, whereas cortisol was significantly higher during ad lib smoking than during abstinence and tended to be highest in the mid-to-late follicular phase. Further investigation will be needed to determine the functional significance of these findings for understanding and treating smoking in women.

The present report examines efforts to elucidate the role of opioid mechanisms in the reinforcement of smoking. A number of approaches have been used to evaluate nicotine-opioid interactions. Opiate agonists such as heroin or methadone have been found to increase cigarette smoking reliably in humans, and morphine has been shown to increase the potency and efficacy of nicotine in rats. There is also an extensive literature documenting the nicotine-stimulated release of endogenous opioids in various brain regions involved in the mediation of opiate reinforcement. Blockade studies using opioid antagonists have not been as conclusive. Although animal models have demonstrated commonalities between nicotine withdrawal and the opiate abstinence syndrome, including reversibility by morphine, and although the impact of nicotine on certain response systems such as respiratory reflexes has clearly been shown to involve opioid mediation, attempts to demonstrate opioid modulation for the key indicators of smoking reinforcement—cigarette consumption and nicotine self-administration—have been fraught with difficulty. Resolution of the apparent contradictions will require taking into account: (a) the biphasic properties of nicotine-opioid effects at higher doses and anti-opioid effects at lower doses; (b) the contributions of the opioid receptor populations — mu, kappa, sigma — stimulated at various dose levels; (c) the possibility that endogenous-opioid activity is entrained primarily during the acquisition or re-acquisition of nicotine self-administration; (d) the possibility that the endogenous opioid response does contribute to nicotine reinforcement but only as a delimited component of the neuroregulatory cascade of nicotine; and (e) the possibility that opioids contribute primarily to nicotine reinforcement under special conditions such as stress. Taking these considerations into account should allow studies on endogenous opioid effects to begin to do justice to the complexity of both smoking behavior and the actions of nicotine.

The effect of fluoxetine hydrochloride, a 5-HT uptake inhibitor (60 mg/day PO), in preventing weight gain associated with nicotine reduction was investigated in participants in a double-blind, placebo-controlled smoking-cessation trial. A lunch of cheese pizza and chocolate bars was offered, and caloric intake was monitored. The analysis focused on subjects (placebo: n = 11; fluoxetine: n = 10) who succeeded in reaching cotinine levels of less than 50% of their starting cotinine levels (signifying a stringent reduction in nicotine intake) and who participated in pre- and post-nicotine reduction lunch sessions 70 days apart. Subjects on placebo gained significantly more weight (mean +/- SEM = +3.3 +/- 0.7 kg) than subjects on fluoxetine (-0.6 +/- 1.2 kg). In fluoxetine-treated subjects, weight gain/loss was strongly correlated with initial body mass index, with higher BMI being associated with greater decreases in weight. A trend towards decreased caloric intake in the fluoxetine group was observed; the change in total calories at lunch was significantly correlated with weight change, an association accounted for principally by change in pizza intake. We conclude that fluoxetine treatment effectively prevents the weight gain that accompanies nicotine reduction and that this phenomenon is mediated, at least in part, by diminished caloric intake.

The impact of nicotine on the central nervous system is, in an important sense, neuroregulatory, with cascading effects on physiological and biochemical function as well as on behavioral activity. Accordingly, the neurotransmitter and neuroendocrine effects of nicotine constitute a critical part of its biological action, which includes reinforcing as well as pathophysiological consequences. This review focuses on nicotine's effects on cholinergic and non-cholinergic nicotine receptors and on the responses of catecholamines, monoamines, hypophyseal hormones, and cortisol. The contribution of critical variables, such as timing and duration of neuroregulator release and the patterns that make up the total response, is still largely unknown, particularly with regard to the effects of environmental context, history of nicotine use, and mode of administration. The evidence suggests that by altering the bioavailability of the above-listed neuroregulators, nicotine serves as a pharmacological "coping response", providing immediate though temporary improvement in affect or performance in response to environmental demands. Much of what is known to date is based on studies involving the administration of agonists and antagonists under different environmental conditions. Newer technological approaches such as autoradiography and positron emission tomography show potential for determining the neuroregulatory patterns involved and specifying nicotine's locus of action relevant to its behavioral and physiological effects.