The effects of smoking on acoustic prepulse inhibition in healthy men and women

Acoustic prepulse inhibition (PPI) refers to the reduction of the startle reflex to an intense stimulus if it is preceded by a weak stimulus. Nicotine and smoking have been reported to enhance PPI in rats and in healthy men, respectively. We studied the influence of smoking on PPI in healthy men and women, comparing non-smokers, deprived smokers, and smokers smoking during the test session after deprivation or after ad libitum smoking. Smoking during the session enhanced PPI, without affecting startle reaction or habituation over time. In addition, the effect of smoking on PPI was gender dependent. In men, ad libitum smoking enhanced PPI compared with non-smokers, while, in women, deprivation reduced PPI and smoking restored PPI to the level of non-smokers. Received: 24 July 1997/Final version: 19 November 1997     

The effects of smoking high nicotine cigarettes on prepulse inhibition, startle latency, and subjective responses

RATIONALE: Several previous investigations with animals and humans have suggested that nicotine enhances prepulse inhibition of the startle reflex (PPI). However, the administration of nicotine activates mesolimbic dopamine, and activation of mesolimbic dopamine is known to attenuate prepulse inhibition of the startle reflex (PPI), which might suggest that nicotine would decrease PPI. OBJECTIVE: The primary aim of this study was to test rigorously the effects of smoking high nicotine cigarettes on PPI and other measures (e.g., heart rate, craving, and mood) when the concentration of nicotine peaks in the brain (i.e., immediately after smoking). METHODS: Thirty smokers participated in two experimental sessions 1 week apart. Two high nicotine cigarettes were smoked in one session, and two control cigarettes were smoked in the other session after overnight deprivation. RESULTS: The results indicated that smoking the high nicotine cigarettes decreased PPI and that PPI increased across trials in both conditions. The interaction between nicotine dose and trial was not significant, although it appeared that high nicotine may have reversed an increase in PPI across trials in the control condition. High nicotine cigarettes also significantly increased heart rate, decreased the latency to peak startle response on control trials, but did not alter the magnitude of the startle response. DISCUSSION: The findings suggest that either high nicotine cigarettes reduced PPI, or possibly, that high nicotine cigarettes may have reversed an increase in PPI across trials as evident in the control condition.     

Effects of caffeine on sensorimotor gating of the startle reflex in normal control subjects: impact of caffeine intake and withdrawal

RATIONALE: Prepulse inhibition (PPI), a cross-species measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. This study was designed to assess caffeine effects on PPI in normal humans, as part of an effort to understand cross-species differences and similarities in the neurochemical regulation of PPI. METHODS: Startle was measured during a screening session; 7 days later, subjects were retested after placebo or caffeine (200 mg; double-blind design). Subjects were characterized as low versus high caffeine drinkers based on established scales (range 11-628 mg/day), and either maintained ad libitum caffeine intake (Ad lib study; n=18) or refrained from caffeine consumption for > or =15 h prior to testing (Withdrawal study; n=12). Autonomic and self-rating measures, acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in divided sessions for 3 h post-treatment. RESULTS: There were significant effects of caffeine and/or caffeine withdrawal on several self-rating and autonomic measures, and on startle reflex habituation, but not on acoustic or tactile startle magnitude or PPI. Difference scores of startle data from screening versus test days revealed no group effects on startle magnitude, but PPI difference scores revealed that caffeine had opposite effects on low versus high caffeine drinkers (means=57 versus 258 mg/day) in the two withdrawal states. In the absence of withdrawal, caffeine reduced PPI in heavy caffeine drinkers; during withdrawal, caffeine increased PPI in heavy caffeine drinkers. The opposite pattern was evident in low caffeine drinkers. CONCLUSIONS: While a physiologically active dose of caffeine has no simple effects on PPI in normal humans, both withdrawal states and normal levels of caffeine consumption may be important factors in understanding this drug's effects on sensorimotor gating.     

Effect of cigarette smoking on prepulse inhibition of the acoustic startle reflex in healthy male smokers

The present study investigated the effects of cigarette smoking on prepulse inhibition (PPI) of the acoustic startle reflex in healthy men. Cigarette smoking in a group of overnight smoking-deprived smokers increased PPI as compared to the smoking-deprived condition. This finding is consistent with previous animal studies showing that nicotine increases PPI of the acoustic startle reflex. In addition, cigarette smoking also reduced startle amplitude during the first 6–7 min of the post-smoking session. Received: 4 March 1996 / Final version: 17 June 1996     

Sweet taste preference in women smokers: Comparison with nonsmokers and effects of menstrual phase and nicotine abstinence

Cigarette smokers weigh less than comparably aged nonsmokers, and many gain weight following cessation. Though some evidence suggests that nicotine reduces food intake, with a selective effect on sweet-tasting foods, the issue remains unresolved. In the current study, 64 women (20 smokers, 26 never-smokers, and 18 ex-smokers) were tested for sweet taste preference; 9 of these smokers were studied under conditions of both ad lib smoking and overnight abstinence, in three hormonally verified menstrual phases. 1) Although no overall differences were detected in taste preference among the three groups, significantly more smokers than nonsmokers preferred the higher sucrose concentrations. 2) No significant differences due to menstrual phase were observed. 3) Although preference ratings did not differ significantly between overnight abstinence and ad lib smoking, a subset of smokers who preferred higher sucrose concentrations rated their preference for the solutions significantly higher during the ad lib smoking sessions. Our findings suggest that smoking and nonsmoking women differ with respect to taste preference and that, at least in a subset of female smokers, preference is affected by nicotine abstinence/acute dosing.     

Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence

The present study was designed to examine the effect of cigarette smoking and withdrawal on working memory. Participants included 15 smokers and 22 matched non-smokers. For both groups the N-Back Task (of working memory) was administered in two test blocks on each of two days. On one day, smokers were tested after >or=13 h abstinence; on the other day, testing began or=13 h but not 相似文献   

Effects of selegiline (l-deprenyl) during smoking and short-term abstinence

RATIONALE: Changes in dopamine level are thought to play an important role in both smoking reward and withdrawal symptoms during abstinence. Medications that modulate dopamine levels may have beneficial effects on both withdrawal symptom levels and on response to smoking lapses during abstinence. OBJECTIVES: To examine the effects of the selective MAO-B inhibitor selegiline on withdrawal symptoms, smoking behavior and smoking satisfaction ratings. METHODS: Fifteen smokers received selegiline (10 mg/day) and placebo (in counterbalanced order) on Monday through Thursday of 2 study weeks, separated by a 2-week washout. During each study week, ad lib smoking sessions were scheduled to assess smoking behavior both before and after a brief period of abstinence. Subjective withdrawal symptoms and mood were measured daily, and a modified Stroop test sensitive to withdrawal was scheduled during the period of abstinence. RESULTS: Selegiline decreased craving, especially during abstinence, and impaired performance on the modified Stroop test during subjects' attempts to abstain. Medication also reduced number of cigarettes smoked and smoking satisfaction ratings during the smoking sessions both before and after the brief abstinence attempt. CONCLUSION: These results are consistent with an important role of dopamine in smoking behavior and abstinence. They suggest that pharmacological reduction of MAO-B levels during the early part of a quit attempt may aid in smoking cessation.     

Role of abstinence and visual cues on food and smoking craving

This study was designed to examine the relationship between cravings for food and cravings for cigarettes by presenting smoking-related or food-related visual cues to smokers who were either smoking-deprived or food-deprived. Fifteen regular cigarette smokers participated in this four-session, within-subject study in which they rated their craving for cigarettes and craving for food under four conditions: after abstaining from smoking, after abstaining from eating, after abstaining from both smoking and eating, or after no abstinence. We found that before presentation of the cues, overnight smoking abstinence increased craving for cigarettes, and overnight food abstinence increased craving for food. In each condition, presentation of cues further increased craving for the object of deprivation: smoking cues further increased craving for cigarettes after smoking abstinence, and food cues further increased craving for food after abstaining from food. Smoking abstinence did not affect craving for food, but food abstinence modestly increased smoking craving. These results indicate that craving for cigarettes or food is specifically increased by both deprivation from the substance and by presentation of substance-related cues.     

Hormonal and subjective effects of smoking the first five cigarettes of the day: a comparison in males and females.

The effects of smoking normal-nicotine-delivery cigarettes on serum cortisol, plasma beta-endorphin (BE), and mood were measured in 8 male and 8 female smokers; 8 male and 8 female nonsmokers served as sham-smoking controls. Smoking five cigarettes of the smokers' usual type after overnight deprivation, either ad lib or via a quantified smoke delivery system, produced small but reliable elevations in serum cortisol concentrations; BE was elevated somewhat after two, but not after four or five cigarettes. Smoking-induced elevations in serum cortisol were correlated with decreases in self-reported drowsiness after two and five cigarettes. Additionally, female smokers reported more drowsiness at baseline and after smoking nicotine-free cigarettes than did male smokers or female nonsmokers. Results suggest that smoking-induced elevations in serum cortisol, which persist for at least the first five cigarettes of the day, may modulate the arousing effects of smoking under conditions of low arousal. Also, nicotine-deprived female smokers may experience subnormal arousal compared to male smokers or female nonsmokers.     

Delay discounting and the behavioural economics of cigarette purchases in smokers: the effects of nicotine deprivation

RATIONALE: In smokers, nicotine deprivation may increase impulsive decision-making and the demand for cigarettes. OBJECTIVES: To investigate the effects of acute nicotine deprivation on (a) the delay discounting of monetary and cigarette rewards, and (b) the behavioural economics of hypothetical cigarette purchases. MATERIALS AND METHODS: A repeated measures design was employed, with participants (daily cigarette smokers, N=30) repeating experimental tasks in two different sessions, once after at least 13 h of abstinence from smoking and once after ad lib smoking. Participants completed measures of cigarette craving, impulsivity, delay discounting and a behavioural economic simulation in which participants made hypothetical purchases of cigarettes and other commodities as the price of cigarettes was systematically varied. RESULTS: Participants showed more pronounced delay discounting of both cigarette and monetary rewards after abstinence compared to after ad lib smoking. In the behavioural economic simulation, nicotine deprivation had no influence on hypothetical cigarette purchases. However, spending on some commodities (alcohol, clothing, household goods, leisure activities and long-distance travel) was reduced as the price of cigarettes increased in order to fund increased spending on cigarettes, although the number of packs of cigarettes purchased actually decreased. CONCLUSIONS: Nicotine deprivation increases impulsive choices for both cigarette and monetary rewards in a delay-discounting task. Results from a behavioural economic simulation suggest that increases in the price of cigarettes may increase smokers' spending on cigarettes, while also reducing the number of cigarettes purchased.     

Effects of atomoxetine on subjective and neurocognitive symptoms of nicotine abstinence

Nicotine dependence has been linked to attention-deficit hyperactivity disorder (ADHD) symptoms in both clinical and general populations. This behavioural pharmacology study used a within-subject, double-blind, crossover design to test the effects of atomoxetine, a medication for ADHD, on nicotine abstinence symptoms. Fifty non treatment-seeking smokers (>/=15 cigarettes/day) completed a baseline session when they were smoking as usual and then two laboratory testing sessions after overnight abstinence and treatment with 7 days of either atomoxetine (1.2 mg/kg) or placebo. During each laboratory session, participants completed subjective measures of abstinence symptoms and performed neurocognitive tasks. In mixed effects models, atomoxetine, compared with placebo, was found to be associated with a reduction in abstinence-induced subjective withdrawal symptoms. Atomoxetine was also associated with significant reductions in self-reported smoking urges amongst smokers who scored high on a baseline measure of smoking for stimulation. However, atomoxetine had no effect on any of the cognitive tasks employed in the study. Thus, atomoxetine may reduce cravings to smoke among smokers who use nicotine to increase arousal.     

Acute cigarette smoking reduces latencies on a Smoking Stroop test

Rationale

Sensitivity to addiction-related cues, a type of attentional bias, may interfere with executive functions that are important in sustaining abstinence from drug abuse. Assessments of attentional bias in research participants who smoke cigarettes have used Smoking Stroop tasks, which are variations of emotional Stroop tasks in which the stimuli are smoking-related and neutral words.

Objectives

We aimed to determine the effect of resumption of smoking by deprived cigarette smokers on attentional bias.

Methods

Testing occurred twice on each of two test days. One test day began after overnight abstinence (13–16 h) and the other after < 1 h of abstinence. The participants (n = 51) smoked a cigarette between the two test sessions on each test day.

Results

Smokers exhibited attentional bias for smoking-related words and had longer response times after overnight abstinence than after brief abstinence. Cigarette smoking between sessions reduced response times on both test days with no interaction by stimulus type.

Conclusions

Smoking-related cues have distracting effects in smokers, and smoking reduces response latency, with no specific effect on attentional bias. The increase in response speed may contribute to a smoker's impression that abstinence hinders performance and that smoking reverses impairment.     

Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia

The prevalence of tobacco smoking is known to be higher in patients with schizophrenia than other psychiatric disorders and general population. These patients also show reduced prepulse inhibition (PPI) of the startle response. PPI refers to a reduction in response to a strong startling stimulus if preceded shortly by a stimulus of sub-threshold intensity. PPI is thought of as an objective index of sensorimotor gating. Nicotine administered subcutaneously or via cigarette smoking enhances PPI in healthy human beings. It also enhances PPI at low, but not high, doses in the rat. We examined the influence of smoking on PPI of the acoustic startle response in 46 male patients with chronic schizophrenia. In a naturalistic design, patients (n = 9) who smoked a cigarette less than 10 min prior to being tested on PPI were compared with other smoking (n = 23) and non-smoking patients (n = 14). We found that the group of patients who smoked a cigarette prior to being tested had significantly greater PPI than other two groups. These observations suggest a PPI-enhancing effect of cigarette smoking on PPI in patents with schizophrenia. Higher prevalence of cigarette smoking in schizophrenic patients may reflect an attempt to improve sensorimotor gating deficits. Copyright 2001 John Wiley & Sons, Ltd.     

Human aggressive responding during acute tobacco abstinence: effects of nicotine and placebo gum

Aggressive and point maintained operant responding of heavy nicotine dependent male tobacco smokers were measured during five 25-min sessions conducted over an 8-h period. Responding under three tobacco abstinence conditions was compared to responding during a baseline condition of ad libitum smoking of the subject's preferred brand of cigarettes. The three tobacco abstinence conditions were: (1) placebo gum, (2) nicotine gum or (3) no gum. Under placebo and nicotine gum conditions, subjects were given two pieces of placebo or 2 mg nicotine gum to chew for 30 min prior to each session. Expired air carbon monoxide (CO) levels were measured at the end of each session to monitor smoking under baseline conditions and compliance with non-smoking requirements under abstinence conditions. Aggressive responding was increased in no gum and placebo gum conditions, with the highest frequency of aggressive responding occurring under no-gum conditions. Aggressive responding during nicotine gum conditions did not differ from baseline ad libitum tobacco smoking. Point maintained responding was either not affected or decreased under placebo and no-gum conditions. These results provided objective data consistent with clinical reports of increased irritability among dependent tobacco smokers during acute tobacco abstinence.     

Expectancy for negative affect relief due to smoking may not be predictive under acute mood situations

Smoking behavior may be more persistent among those who expect that smoking will relieve negative affect (NA). Assessing smoking expectancies temporally close to mood situations could enhance the predictive value of that assessment. Dependent smokers (n = 71; 43 male, 28 female) participated in five laboratory sessions, each involving mood induction. The NA relief scale of the Smoking Consequences Questionnaire-Adult (SCQ-A), a very common measure of smoking expectancies during hypothetical situations, was assessed during initial screening. The SCQ-A was compared with a modified acute version administered each session, in which items asked about immediate expectancy for NA relief by smoking "right now" (termed Immediate Negative Affect Relief, or INAR). Actual NA relief due to smoking was measured each session by change on the NA scale of the Diener & Emmons Mood Form. The five sessions (counterbalanced) involved three different negative mood tasks, the negative mood condition of overnight smoking abstinence, and neutral mood (control). Generalized estimating equations showed that temporal proximity to the mood situation slightly enhanced the ability of expectancy to predict actual change in NA due to smoking, as the interaction with condition was significant for the INAR but marginal for the SCQ-A. However, the acute INAR predicted NA relief due to smoking only after overnight smoking abstinence and not during the other specific mood induction conditions, contrary to expectations, while the SCQ-A was not significant during any of the individual conditions. In sum, assessment of expectancy for NA relief may be of limited use in predicting actual NA relief from smoking during a current mood situation, aside from NA due to overnight abstinence.     

A nicotine dependent and a nicotine independent component of smoking related pulse and activity variation

In a field study, heart rate and motor activity were continuously assessed during two days in smokers, abstinent smokers and non-smokers. Smoking abstinence reduced heart rates by about 10 bpm to the non-smoker level without affecting motor activity. Averaging heart rate and activity using lighting of the cigarettes as the triggering event revealed the characteristic profiles described previously. Both variables increased during the last five minutes before lighting the cigarettes and decreased immediately upon lighting to near or even below the prelighting levels. This lighting response was maintained in a similar fashion when the subjects marked the time points of the desire for smoking but omitted lighting the cigarettes and it remained highly similar for the first and last five cigarettes of the day. In non-smokers a similar pattern was also obtained using the first sip of coffee as triggering event. In smoking smokers, this lighting response was followed by an increase of heart rate without changes in activity. In contrast to the lighting response, this smoking related increase of heart rate disappeared for the last five as opposed to the first five cigarettes of the day, and it was also absent for ‘imaginary’ smoking without lighting.     

Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking

Separate and combined effects of nicotine and the nicotinic antagonist mecamylamine were studied in 32 healthy volunteer smokers after overnight abstinence from smoking. Subjects participated in three sessions (3 h each), during which they wore skin patches delivering either 0 mg/24 h, 21 mg/24 h or 42 mg/24 h nicotine. Thirty-two subjects were randomly assigned to two groups receiving oral mecamylamine hydrochloride (10 mg) vs. placebo capsules. Two and one-half hours after drug administration, subjects were allowed to smoke ad lib, rating the cigarettes for rewarding and aversive effects. Transdermal nicotine produced a dose-related reduction in the subjective rewarding qualities of smoking. Nicotine also reduced craving for cigarettes and this effect was attenuated, but not eliminated, by mecamylamine. Mecamylamine blocked the discriminability of high vs. low nicotine puffs of smoke, and increased nicotine intake substantially during the ad lib smoking period. Some of the psychophysiological effects of each drug (elevation in blood pressure from nicotine, sedation and decreased blood pressure from mecamylamine) were offset by the other drug. The results supported the hypothesis that nicotine replacement can alleviate tobacco withdrawal symptoms even in the presence of an antagonist such as mecamylamine. Mecamylamine did not precipitate withdrawal beyond the level associated with overnight cigarette deprivation, suggesting its effects were primarily due to offsetting the action of concurrently administered nicotine as opposed to blocking endogenous cholinergic transmission.     

Regional brain activity correlates of nicotine dependence.

Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerstr?m Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction.     

Matching strategies for drug studies of prepulse inhibition in humans

Prepulse inhibition (PPI), a measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders. Animal studies have revealed drug effects on PPI that may be relevant to understanding the biology of gating deficits in human populations. Recent efforts have examined similarities and differences in drug effects on PPI between rodents and humans. Experimental designs are needed that most effectively translate these drug studies across species. In the course of a larger set of studies of drug effects on startle in normal human subjects, we examined the potential utility of one design element that is utilized in rodent PPI drug studies: pre-testing to diminish variability across dose groups. Startle was measured during a screening session; 7-10 days later, 20 subjects were retested after consuming a placebo pill. Acoustic and tactile startle, and unimodal and cross-modal PPI, were measured in five sessions over a period of 3 hours post-placebo. There were significant and robust correlations between levels of startle magnitude and PPI during pre-testing and testing, for both left and right eyeblink measures. Comparable correlations were evident for both unimodal and cross-modal testing. Pre-testing values were most predictive of test performance early in the 3-hour test session, and predictive strength diminished or disappeared towards the end of testing. The utility of a pre-testing design could be seen clearly by comparing groups 'matched', based on pre-test data, versus groups created by alternating or random group assignments. It is concluded that pre-test designs can effectively match groups with comparable levels of startle or PPI, and thereby diminish between-group variability in human PPI drug studies. For studies using repeated testing to assess drug time course, the predictive value of pre-testing is greatest in early test sessions.     

Nicotine blood levels and subjective craving for cigarettes

This study examined cigarette craving and blood nicotine levels in 11 male heavy smokers who were observed during 16 h of tobacco abstinence. Subjects rated their urge to smoke on a new brief 10-item questionnaire, Urge to Smoke (UTS), Schuh and Stitzer's four-item Visual Analog Scale (SSI), and a Strength of Urge to Smoke (SUTS) item. Testing occurred: 1) after 16 h (1700 h the night before to 0900 h the next morning) of abstinence from smoking; 2) after an ad lib smoking period following the 16 h abstinence; 3) every hour during 6 hours of abstinence; 4) and finally, after the 6 h abstinence, another ad lib smoking period. Thus, subjects smoked twice in each session. Blood plasma nicotine levels were measured before, after, and every 2 h during the 6-h abstinence period for a total of six measures. Blood pressure and heart rate were measured prior to each blood draw. There was a significant negative correlation between blood nicotine levels and craving for cigarettes on all craving questionnaires (rs = -0.55 to -0.78; ps < 0.002). Carbon monoxide was shown to correlate highly with nicotine blood levels (rs = 0.83 to 0.98 across subjects; ps < 0.001). Results are consistent with the hypothesis that "urge to smoke" reflects nicotine seeking in continuing smokers.