The separate and combined effects of nicotine and alcohol on working memory capacity in nonabstinent smokers.

Research indicates that nicotine and alcohol are often used on the same occasion. However, the reasons for their concurrent use are not well understood. We hypothesized that one reason smokers use tobacco when they drink alcohol is to compensate for alcohol’s negative effects on processing capacity with nicotine’s enhancement of processing capacity. As such, the present study tested this theory by using an independent groups design to examine the separate and combined acute effects of alcohol and nicotine on working memory (WM) capacity. Nonabstinent daily smokers (n = 127) performed the counting span task (CSPAN) after consuming either an alcohol (men: 0.8 g/kg; women: 0.7 g/kg) or placebo beverage and smoking either nicotinized (1.14 mg nicotine, 15.9 mg tar) or denicotinized (.06 mg nicotine, 17.9 mg tar) cigarettes. Analyses revealed that smokers who smoked the nicotinized cigarettes performed significantly worse on the CSPAN task than smokers who smoked the denicotinized cigarettes. Although there was no main effect of alcohol on WM performance, women exhibited better WM performance than men after consuming alcohol whereas men performed better than women on the WM task after consuming the placebo beverage. Findings also revealed no interaction between the two substances on WM performance. Taken together, results suggest that nicotine impairs nonabstinent smokers’ verbal WM capacity and that gender moderates the effects of alcohol on WM. Furthermore, the present findings failed to support the notion that nicotine compensates for alcohol-related decrements in working memory capacity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The influence of transdermal nicotine on tobacco/nicotine abstinence and the effects of a concurrently administered cigarette in women and men.

Transdermal nicotine (TN) is an efficacious smoking cessation pharmacotherapy thought to work, in part, by attenuating the effects of tobacco/nicotine abstinence and the effects of concurrently smoked cigarettes. Clinical trials suggest that TN may be less efficacious for women. This study explored the possibility of TN-related gender differences in ≥8 hour abstinent smokers (54 women, 70 men) who completed four within-subject, double-blind, placebo-controlled sessions corresponding to 0, 7, 14, and 21 mg TN. In each approximately 6.5-hr long session participants smoked an own-brand cigarette 4 hours after TN administration and physiological and subjective outcomes were examined throughout each session. Results revealed that TN suppressed some signs and symptoms of tobacco abstinence and attenuated some effects of smoking, and these effects were not dependent on gender. Women were more sensitive to the direct effects of nicotine (e.g., ratings of Nauseous) and, independent of TN dose, self-administered less nicotine when smoking and rated smoking as less rewarding. Thus, although this study does not shed light on clinical observations that TN is less effective for women, results suggest that TN might need to be combined with other interventions to supplement its effects on tobacco/nicotine abstinence and concurrent smoking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of oral caffeine pretreatment on response to intravenous nicotine and cocaine.

Previous research suggests that under conditions of chronic daily caffeine administration, caffeine increases the effects of nicotine. Little is known about the effects of caffeine pretreatment on response to nicotine under infrequent caffeine administration conditions. The present study examined whether infrequent (not on consecutive days) acute oral caffeine administration alters subject-rated, physiological, and monetary value effects of intravenous nicotine in regular users of caffeine, tobacco, and cocaine. To determine the specificity of effects of caffeine on response to nicotine, the effects of caffeine administration on response to intravenous cocaine (another short-acting stimulant) were also studied. Fourteen (1 woman) volunteers participated in this 3–4 week, double-blind, inpatient study. Volunteers participated in 10 experimental conditions in pseudo-randomized order, in which oral caffeine (250 mg/70 kg) or placebo was administered 1 hr before an intravenous injection, consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline. Infrequent acute caffeine pretreatment attenuated the increase resulting from 2 mg/70 kg nicotine administration on ratings of “rush,” “good effects,” “liking,” “high,” and “drowsy/sleepy.” Caffeine had no significant effect on physiological response to nicotine. Caffeine had no significant effect on subject-rated and physiological response to cocaine, with the exception that caffeine significantly augmented blood pressure response to cocaine. In contrast to the previous research using chronic caffeine maintenance, these data suggest that infrequent acute caffeine administration may attenuate nicotine effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pain inhibition, nicotine, and gender.

The ability of nicotine to decrease sensitivity to pain in humans has been a subject of dispute. Decreased sensitivity has been demonstrated in studies involving men, whereas the effect has been less obvious or absent in studies involving predominantly, or entirely, women. To determine whether there are gender differences in nicotine's hypoalgesic actions, ratings of electrocutaneous stimulation were obtained from 30 male and 44 female smokers and nonsmokers under placebo and nicotine conditions. Nicotine increased the pain threshold and tolerance ratings of men but had no effect on the pain ratings of women. Among men, there was no effect of smoking history, suggesting that the changes in pain perception reflect a direct pain-inhibitory effect of nicotine rather than a relief from acute nicotine withdrawal. Nicotine had no effect on mood or task ratings, indicating that the antinociceptive effects observed were not due to nicotine's putative mood effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naltrexone alteration of the nicotine-induced EEG and mood activation response in tobacco-deprived cigarette smokers.

The neural mechanisms contributing to the arousal-eliciting actions of smoking and nicotine involve multiple neurotransmitter systems. The current study examined the role of opioid neurotransmission in modulating the neuroelectric- and mood-activating response to acute nicotine administration in overnight tobacco-deprived smokers. In a randomized, double-blind, placebo-controlled design involving 18 (10 male, 8 female) overnight tobacco-abstinent smokers, spectrally analyzed electroencephalographic (EEG) activity and subjective reports of mood, euphoria, and smoking withdrawal were assessed in response to nicotine gum (4 mg) after pretreatment with placebo or with 50 mg of the opioid antagonist naltrexone. In addition to reducing withdrawal symptoms and increasing euphoria ratings, as well as subjective alertness in male participants, nicotine induced an EEG arousal response consisting of diffuse slow wave (delta, theta) amplitude reductions, frontal fast alpha wave amplitude increments, and elevations in beta wave amplitude, which were greater in female than in male smokers. Naltrexone attenuated the alerting and euphoric actions of nicotine but did not affect nicotine's ameliorating effects on withdrawal symptoms. Nicotine-induced frontal reductions in delta and global reductions in theta were prevented by naltrexone pretreatment, as were increases in anterior recordings of relative fast alpha. These findings suggest that the opioid system is involved in nicotine-induced subjective and neuroelectric arousal and implicate opioid-cholinergic interactions in the elicitation of these arousal responses to nicotine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: Role of D2 and D3 receptor subtypes.

Neonatal quinpirole treatment in rats produces increased sensitivity of dopamine D2-like receptors throughout the animal’s lifetime, referred to as D2 priming. There is little information on the effects of nicotine in adolescent rats, especially in a model that has clinical relevance to psychosis where increased D2 receptor sensitivity is common. Male and female rats were treated with quinpirole (1 mg/kg) or saline from postnatal (P) day 1–P21, given nicotine (0.5 mg/kg) or saline from P33 through P49, and placed into a locomotor arena for behavioral testing. Nicotine or saline treatment was preceded by the D2-like receptor antagonist eticlopride, D3 antagonist nafadotride, or saline. Conditioned hyperactivity was analyzed on P50 in the same context in a drug-free test. In females, D2 priming increased the locomotor response to acute nicotine, but did not affect subsequent nicotine sensitization, and only non–D2-primed females demonstrated conditioned hyperactivity. Eticlopride and nafadotride blocked behavioral sensitization, although nafadotride was more effective at blocking nicotine-conditioned hyperactivity in females. In males, D? priming enhanced sensitization to nicotine and produced conditioned hyperactivity, which were blocked by eticlopride and nafadotride. These results have implications for psychosis and comorbidity of nicotine abuse in adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinforcing effects of nicotine as a function of smoking status.

The authors compared acute nicotine self-administration among 4 groups varying in current or past dependence: dependent smokers, nondependent smokers, ex-smokers who had quit at least I year ago, and nonsmokers. Nicotine (0 vs. 12 μg/kg/8 sprays) available by nasal spray was self-administered with a choice procedure. Self-administration also was related to participant characteristics (sex, alcohol and caffeine intake, sensation-seeking score) and to subjective responses to initial nicotine spray exposure. Nicotine self-administration was similar between dependent and nondependent smokers but was greater in those groups than in ex-smokers and nonsmokers, who did not differ from each other. Self-administration was unrelated to most other participant characteristics. In nonsmokers, self-administration was related directly to pleasurable effects but inversely to aversive effects. Few effects were related to self-administration in the other groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of estradiol and progesterone in modulating the subjective effects of stimulants in humans.

Although stimulant abuse is a growing problem among women, few studies have focused on factors that may be implicated in potential sex differences. Numerous preclinical studies have indicated that female rodents are more sensitive than male rodents to the behavioral effects of stimulants and that the hormone estradiol is involved in these sex differences. In humans, the subjective response to stimulants is greater in the follicular phase (characterized by moderate estradiol levels and minimal progesterone levels) than in the luteal phase (characterized by elevated estradiol levels and elevated progesterone levels). Differences between men and women emerge only when men are compared with women in the luteal phase; the subjective response to stimulants is similar in men and women in the follicular phase. In contrast to rodents, there is minimal evidence that estradiol enhances the subjective response to stimulants in humans. Rather, the hormone progesterone has been shown to attenuate the subjective response to stimulants, particularly in women. Recent preclinical data confirm that progesterone reduces the behavioral response to stimulants. In summary, there is converging evidence from studies in humans that (a) men and women do differ in their subjective response to stimulants; (b) these sex differences are evident when women are in the luteal phase, when progesterone levels are elevated; and (c) progesterone administration attenuates the subjective response to stimulants. Therefore, the menstrual cycle should be addressed in mixed-gender studies. Moreover, the modulatory effects of progesterone on reducing the positive effects of cocaine may have some clinical utility in treating stimulant abusers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of progesterone in nicotine addiction: Evidence from initiation to relapse.

Nicotine addiction continues to be the main cause of preventable death in developed countries. Women and teen girls appear to be more vulnerable on certain aspects of nicotine addiction compared with men and boys. While the mechanism of gender differences in nicotine addiction is not yet clear, evidence suggests that while estrogen may underlie enhanced vulnerability in females, progesterone may protect females. Thus, progesterone may have therapeutic use for tobacco addiction, especially in female smokers. A greater understanding of the role of progesterone in nicotine addiction is important not only from a treatment standpoint, but also from a prevention standpoint: hormone transition phases, such as those that occur at adolescence, and during pregnancy and following birth, as well as following hormonal manipulation (e.g., using methods of hormonal birth control), may all contribute to changes in vulnerability to nicotine addiction. In this review, we summarize recent evidence from clinical and preclinical studies examining the role of progesterone in nicotine addiction focusing on its role during initiation of use and during later phases of the addiction process as a potential relapse prevention treatment. We conclude with future directions including further examination of progesterone as a potential intervention and treatment of nicotine addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gender differences and developmental change in externalizing disorders from late adolescence to early adulthood: A longitudinal twin study.

Using data from over 1,000 male and female twins participating in the Minnesota Twin Family Study, the authors examined developmental change, gender differences, and genetic and environmental contributions to the symptom levels of four externalizing disorders (adult antisocial behavior, alcohol dependence, nicotine dependence, and drug dependence) from ages 17 to 24. Both men and women increased in symptoms for each externalizing disorder, with men increasing at a greater rate than women, such that a modest gender gap at age 17 widened to a large one at age 24. Additionally, a mean-level gender difference on a latent Externalizing factor could account for the mean-level gender differences for the individual disorders. Biometric analyses revealed increasing genetic variation and heritability for men but a trend toward decreasing genetic variation and increasing environmental effects for women. Results illustrate the importance of gender and developmental context for symptom expression and the utility of structural models to integrate general trends and disorder-specific characteristics. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anxiety sensitivity and panic reactivity to bodily sensations: Relation to quit-day (acute) nicotine withdrawal symptom severity among daily smokers making a self-guided quit attempt.

The current investigation explored the main and interactive effects of panic attacks in response to laboratory-induced bodily sensations and anxiety sensitivity in predicting acute nicotine withdrawal symptoms among daily smokers making a self-guided quit attempt. Participants were 99 daily smokers (58% women; Mage = 28.4 years, SD = 11.7) who completed a battery of questionnaires, a voluntary hyperventilation challenge, and a measure of nicotine withdrawal symptoms 12 hr after making a self-guided quit attempt. Results indicated that the interaction of anxiety sensitivity and panic responsivity to the challenge predicted quit-day nicotine withdrawal symptom severity above and beyond the main effects (p     

Daily Processes in Stress and Smoking: Effects of Negative Events, Nicotine Dependence, and Gender.

The author used a multilevel daily process design to examine relations among daily negative events, perceived stress, smoking, and smoking urges. The moderating effects of gender and nicotine dependence were also explored. Fifty-one adult community-residing smokers recorded negative events, perceived stress, cigarette smoking, and urges to smoke 4 times daily for 14 days. Analyses of within-person relations showed that participants smoked more cigarettes and experienced more urges to smoke on occasions with higher numbers of negative events and higher levels of perceived stress. These relations were stronger for men than for women. Nicotine dependence did not interact with events or stress in predicting smoking or urges. These findings build on laboratory studies and cross-sectional surveys by showing that in naturalistic settings, occasions with negative events and perceived stress are associated with smoking and urges to smoke. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotine dependence subtypes among adolescent smokers: Examining the occurrence, development and validity of distinct symptom profiles.

To increase understanding of the etiology and epidemiology of nicotine dependence among adolescent smokers, the present study examined the occurrence and development of distinct nicotine dependence symptom profiles in a sample of adolescent smokers. A total of 25 secondary schools throughout the Netherlands participated in a 1-year longitudinal study. Multiple dimensions of nicotine dependence were assessed, at two time points, among 641 adolescents (aged 14–17 years) who were classified as smokers. Results showed 4 distinct, yet stable, nicotine dependence subtypes that could be characterized by quantitative as well as qualitative differences. The symptom profiles were similar for males and females but differentially associated with previously identified correlates of nicotine dependence, namely parental smoking, peer smoking, and depressive mood. Finally, differential links of the 4 subtypes were found with regard to smoking uptake and cessation. The finding of qualitative different subgroups of adolescent smokers may have important implications for intervention efforts regarding nicotine dependence and smoking cessation. Such efforts may need to be tailored to the specific subgroups’ needs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cigarette abstinence impairs memory and metacognition despite administration of 2 mg nicotine gum.

The authors assessed the effects of cigarette abstinence (nonabstinent vs. minimum 8 hours abstinent) and nicotine gum (0 mg vs. 2 mg nicotine) on sustained attention, free recall, and metacognition using a within-subjects design. Moderate smokers (10 women and 22 men) received one training session followed by four test sessions on consecutive days. Nicotine gum improved sustained attention in both abstinent and nonabstinent states, but had no significant effect on predicted or actual recall levels. Cigarette abstinence significantly impaired free recall and reduced the magnitude of participants' predictions of their own performance. In addition, participants were significantly more overconfident about their future memory when abstinent. Thus, nicotine gum can improve smokers' performance in basic aspects of cognition (e.g., sustained attention) but may not alleviate the detrimental effects of cigarette abstinence on higher-level processes such memory and metacognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relative impact of nicotine dependence, other substance dependence, and gender on Bechara Gambling Task performance.

Individuals with substance use disorders (SUDs) tend to focus more on immediate, rather than cumulative, consequences of their actions on measures of decision-making. This type of decision-making may contribute to continued substance use. The present study compared the performance of four groups of individuals on one measure of decision-making, the Bechara Gambling Task (BGT). The groups were (a) heavy smokers with comorbid substance dependence (n = 40), (b) heavy smokers with no history of substance dependence (n = 19), (c) substance dependent never smokers (n = 26), and (d) never smokers with no history of substance dependence (n = 34). Analysis revealed that there were no significant main effects of gender or SUD status. However, a significant gender by SUD status interaction was found, such that men with an SUD performed more poorly on the BGT than men without an SUD history. Women with and without an SUD both performed poorly on this task. Unexpectedly, no differences in BGT performance were found between smokers and nonsmokers. Overall, findings indicate that having an SUD, other than nicotine dependence, is correlated with poor BGT performance in men only. The BGT did not differentiate between women with and without SUDs, and therefore, may not be an appropriate measure of decision-making in women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nicotine dependence, depression, and the moderating role of goal cognitions.

The authors examined the moderating role of goal cognitions in the process of nicotine dependence in young adult smokers. A college sample of 85 male and 78 female smokers completed measures of nicotine dependence and psychological distress. They also provided cognitive evaluations for goals related to smoking cessation on scales measuring self-efficacy, value, planning, self-reward, self-criticism, self-monitoring, social comparison, and positive and negative goal-based arousal. As has been previously established, depression had a direct and significant effect on nicotine dependence. Moreover, significant interactions between goal cognitions and depression provided evidence for the hypothesized moderating effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of nicotine on negative affect among more impulsive smokers.

In the present study, the authors tested the hypothesis that nicotine would provide greater relief from negative affect for more impulsive smokers than for less impulsive smokers. Euthymic adult smokers (N=70) participated in 2 laboratory sessions, during which they underwent a negative mood induction (music + autobiographical memory), then smoked either a nicotinized or de-nicotinized cigarette. Mixed-effects regression yielded a significant Impulsivity × Condition (nicotinized vs. de-nicotinized) × Time interaction. Simple effects analyses showed that heightened impulsivity predicted greater negative affect relief after smoking a nicotinized cigarette but not after smoking a de-nicotinized cigarette. These data suggest that nicotine may be a disproportionately powerful negative reinforcer for highly impulsive smokers, promoting higher levels of nicotine dependence and inhibiting smoking cessation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Automatic affective responses to smoking cues.

The authors examined automatic emotional reactions to smoking cues among 35 smokers and 25 nonsmokers (32 women and 28 men), using a novel implicit measure, the Affect Misattribution Procedure. Associative-learning theories of addiction suggest that smokers develop positive responses to cues linked to the rewarding effects of nicotine. Prior research, however, has yielded mixed evidence for whether smokers have favorable or unfavorable automatic responses to smoking cues. These findings may depend on the methods used to measure implicit responses. Using the Affect Misattribution Procedure, the authors found that nonsmokers responded to smoking cues with clear negative affect, whereas smokers' responses depended on individual differences in current smoking withdrawal. Smokers having withdrawal symptoms and those most motivated to smoke showed favorable emotional responses to smoking cues, but those with no withdrawal or low motivation to smoke showed negative responses. These results help integrate previous studies finding that smokers have negative automatic responses to cigarettes with those studies finding that smokers' responses were relatively positive. The results are important for theories that emphasize the role of cue conditioning in maintaining addiction because these theories assume, consistent with the current findings, that smoking cues can take on positive reward value. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Male and female mice differ for baseline and nicotine-induced event related potentials.

The usage patterns and biological effects of cigarette smoking differ significantly among men and women. This study seeks to clarify the interaction that exists between nicotine and biological gender by investigating changes in brain electrical activity after acute nicotine treatment. The P20, N40, and P80 components of the auditory evoked potential were examined in male and female C57BL/6J mice using a paired-stimulus gating paradigm. Consistent with previously published data, acute nicotine resulted in increased gating of the P20 but a decrease in that of N40. Nicotine also resulted in a lengthening of P20 latency but a decrease in that of N40 and P80. The P80 latencies of male and female subjects were differentially affected by nicotine, as males appeared to be more sensitive to its shortening effect. Males and females also exhibited differences in N40 and P80 amplitudes, both of which were smaller in males. The effects of gender on auditory evoked potential amplitude suggest dimorphic signaling in the N40 and P80 generators. Whether this electrophysiological sexual dimorphism has functional consequences for sensory or cognitive abilities requires additional research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex and menstrual cycle differences in the subjective effects from smoked cocaine in humans.

To investigate sex and menstrual cycle effects in response to cocaine administration, data from existing studies were analyzed. First, responses to a single delivery of 0.4 mg/kg smoked cocaine were investigated. Women reported lower ratings for measures of paranoid/suspicious and heart racing/pounding than did men. In addition, women in the luteal phase reported diminished ratings for a measure of feel high than did both women in the follicular phase of the menstrual cycle and men. Second, responses to up to 6 deliveries of 0.4 mg/kg smoked cocaine were investigated. Women, compared with men, had lower ratings on feel high, heart racing/pounding, and feel stimulated. Results suggest that there are significant sex and menstrual phase differences in the subjective effects of cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)