Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease

Rationale: Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer’s disease (AD), but little is known about chronic nicotine effects. Objective: The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer’s disease subjects over a 4-week period. Methods: The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol^®) for 16?h a day at the following doses: 5?mg/day during week 1, 10?mg/day during weeks 2 and 3 and 5?mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy. Results: Nicotine significantly improved attentional performance as measured by the Conners’ continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function. Conclusions: The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer’s disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects.     

Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment

Objectives Chronic transdermal nicotine has been found to improve attentional performance in patients with Alzheimers disease (AD), but little is known about chronic nicotine effects in age-associated memory impairment (AAMI), a milder form of cognitive dysfunction. The current study was performed to determine the clinical and neuropsychological effects of chronic transdermal nicotine in AAMI subjects over a 4-week period.Design The double-blind, placebo-controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period.Setting An outpatient setting was used.Participants The subjects (n=11) met criteria for AAMI.Interventions The subjects were given nicotine patches (Nicotrol) to wear for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during week 2 and week 3 and 5 mg/day during week 4.Measurements The effects of nicotine treatment were determined with the clinical global impressions questionnaire, Conners Continuous Performance test, and the automated neuropsychologic assessment metrics (ANAM) computerized neuropsychology battery.Results Nicotine significantly improved the clinical global impression score as assessed by participants, as well as objective tests of attentional function on the Connors Continuous Performance Test and decision reaction time on the neuropsychology test battery. Nicotine did not improve performance on other tests measuring motor and memory function.Conclusion Chronic transdermal nicotine treatment in AAMI subjects caused a sustained improvement in clinical symptoms and objective computerized tests of attention. These results support the further investigation of nicotinic treatment as a promising therapy for AAMI.     

Nicotine effects on adults with attention-deficit/hyperactivity disorder

Several lines of evidence suggest that nicotine may be useful in treating the symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). The current study was an acute, placebo-controlled double-blind experiment to determine whether nicotine might be useful as an alternative treatment of adults with ADHD symptomatology. Six smokers and 11 nonsmokers who were outpatient referrals for ADHD were diagnosed by DSM-IV criteria. Measures of treatment effect included the Clinical Global Impressions (CGI) scale, Hopkins' symptom check list (SCL-90-R), the Profile of Mood States (POMS), Conners' computerized Continuous Performance Test (CPT), the Stroop test, and an interval-timing task. The smokers underwent overnight deprivation from smoking and were given a 21 mg/day nicotine skin patch for 4.5 h during a morning session. The nonsmokers were given a 7 mg/day nicotine skin patch for 4.5 h during a morning session. Active and placebo patches were given in a counterbalanced order approximately 1 week apart. Nicotine caused a significant overall nicotine-induced improvement on the CGI. This effect was significant when only the nonsmokers were considered, which indicated that it was not due merely to withdrawal relief. Nicotine caused significantly increased vigor as measured by the POMS test. Nicotine caused an overall significant reduction in reaction time (RT) on the CPT, as well as, with the smokers, a significant reduction in another index of inattention, variability in reaction time over trial blocks. Nicotine improved accuracy of time estimation and lowered variability of time-estimation response curves. Because improvements occurred among nonsmokers, the nicotine effect appears not to be merely a relief of withdrawal symptoms. It is concluded that nicotine deserves further clincal trials with ADHD.     

Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms

Nicotine nasal spray and nicotine gum have been found to be effective in relieving nicotine withdrawal symptoms. In this randomized single-blind study, 91 cigarette smokers were randomly assigned to a single 1 mg dose of active nicotine nasal spray (n = 29), active 4 mg nicotine gum (n = 31), saline placebo nasal spray (n = 16) or placebo gum (n = 15). Following overnight abstinence, subjects repeatedly completed visual analog scales for assessing nicotine withdrawal symptoms over 30 min preceding (time -30 min to time 0) and 120 min following a single dose of study medication. This sequence was performed 3 times during the day. Nicotine withdrawal symptoms were assessed on a 41-point visual analog scale (1 = no withdrawal, 41 = extreme withdrawal). At the initial session only, blood samples for serum nicotine levels were taken at baseline, then at 5, 10, 30 and 120 min following study drug administration. The mean (± SD) age of the subjects was 38.6 (±10.1) years, 48% were females, smoking rate was 24.5 (±7.8) cigarettes per day, and years of smoking was 19.9 (±10.0). A single 1 mg dose of nicotine nasal spray provided more immediate relief for craving for a cigarette compared to a single 4 mg dose of nicotine gum. Serum venous nicotine levels for the active nicotine nasal spray and nicotine gum were comparable at 5 and 10 min while the levels were higher for nicotine gum at 30 and 120 min. Changes in withdrawal symptoms were not found to be related to serum venous nicotine levels. Our findings provide a rationale for the as needed use of nicotine nasal spray to control withdrawal symptoms, possibly in combination with other medications with longer acting effects. Received: 18 February 1998/Final version: 1 May 1998     

The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls.

Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n=28) and healthy controls (n=32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebo-controlled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.     

Characterization of tobacco withdrawal symptoms: transdermal nicotine reduces hunger and weight gain

The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects, or by subjects smoking during withdrawal. To reduce these occurrences, 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine (21 mg) or placebo transdermal patches. Subject attrition was low, with 80.5% of participants continuing through the 5-week study period. Abstinence rates were also high over this period (75% and 61% in active and placebo groups, respectively). In this multisite, double-blind trial, withdrawal severity was assessed using a nine-item daily self-report questionnaire, and abstinence was confirmed via CO monitoring. Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes, irritability, anxiety, appetite, sleep disruption, difficulty concentrating, restlessness, depression, and impatience. Treatment with transdermal nicotine reduced craving for cigarettes, anxiety, irritability, and appetite, as well as weight gain (1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups, respectively). Received: 29 June 1995 / Final version: 22 April 1996     

Mecamylamine does not precipitate withdrawal in cigarette smokers

Mecamylamine is an antihypertensive that acts via nicotinic antagonism and has been suggested as an aid in smoking cessation. Nicotine dependent patients may not accept mecamylamine if it precipitates withdrawal, as it does in nicotine dependent rats. This study examined mecamylamine’s effects using procedures designed to measure precipitated withdrawal symptoms in humans. Ten cigarette smokers (mean of 37.5 cigarettes/day) and ten non tobacco-using subjects participated in three 6-h sessions. After a 2-h baseline period in which smokers smoked one cigarette every 30 min, oral mecamylamine (0, 10, or 20 mg randomly ordered across sessions) was administered (double-blind). No smoking was allowed for the remainder of the session. Mecamylamine reduced blood pressure and increased heart rate relative to placebo in both the smokers and the non-tobacco users. No reliable direct subjective effects of mecamylamine were observed. Smokers’ subjective reports of cigarette craving and tobacco withdrawal increased, and DSST performance was disrupted over the last 4 h of each session. Effects were independent of dose (placebo versus active). These results suggest that up to 20 mg mecamylamine will not precipitate nicotine withdrawal and that this medication would be acceptable for use in smoking cessation. Received: 20 April 1996/Final version: 3 June 1996     

Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task

Rationale Nicotinic receptors have been implicated in attentional performance. Nicotine can improve attention in animals and humans, but knowledge about relevant receptor subtypes is very limited.Objectives The aim was to examine the role of α7 receptors in attentional performance of mice and in effects of nicotine.Materials and methods Mice with targeted deletion of the gene coding for the α7 subunit of nicotinic receptors and wild-type controls were trained on a five-choice serial reaction time task with food reinforcers presented under varying parametric conditions. Nicotine was administered in a range of doses (0.001–1.0 mg/kg sc), including those reported to enhance attentional performance.Results Initially the α7^−/− (knockout) mice responded less accurately and made more anticipatory responses. After task parameters were altered so that the time allowed for responding was reduced and anticipatory (impulsive) responses were punished by a time-out, the pattern of performance deficits changed; there were increased omission errors in α7^−/− mice but normal levels of accuracy and anticipatory responding. Nicotine did not improve any measure of performance, either with the original training parameters or after retraining; the largest dose used (1.0 mg/kg) produced a general impairment of responding in α7^−/− and wild-type mice.Conclusions α7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for α7 receptors in attentional processing. However, identification of a protocol for assessing attention-enhancing effects of nicotine in mice may require further modifications of test procedures or the use of different strains of animal.     

Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention

Central cholinergic and adrenergic pathways support the attentional processes necessary for detecting and reporting temporally unpredictable stimuli. To assess the functional effects of pharmacological manipulations of these pathways, male Long-Evans rats performed a two-choice, discrete-trial signal-detection task in which food was provided for pressing one lever after presentation of a signal (a 300-ms light flash), and for pressing a second lever at the end of a trial lacking a signal. Seven signal intensities were presented during each 1-h session in a pseudo-random order across three 100-trial blocks. After acquisition of a stable performance baseline, the acute effects of chlordiazepoxide (0, 3, 5, 8 mg/kg IP), pilocarpine (0, 1.0, 1.8, 3.0 mg/kg SC), scopolamine 0, 0.030, 0.056, 0.100 mg/kg SC), nicotine (0, 0.08, 0.25, 0.75 mg/kg SC), mecamylamine (0, 1.8, 3.0, 5.6 mg/kg IP), clonidine (0, 0.003, 0.010, 0.030 mg/kg SC), and idazoxan (0, 1, 3, 10 mg/kg SC) were assessed. Five measures of performance were analyzed: response failures; the proportion of “hits” [P(hit): the proportion of correct responses on signal trials]; the proportion of “false alarms” [P(fa): the proportion of incorrect responses on non-signal trials]; and response times (RT) for hits and for correct rejections. All drugs which slowed responding affected RT for hits and correct rejections equivalently, suggesting little or no influence of motor slowing on choice accuracy. Chlordiazepoxide reduced P(hit) at low signal intensities only, without affecting P(fa) or RT, consistent with sensory impairment (reduced visual sensitivity). All other drugs except nicotine reduced P(hit) at high signal intensities preferentially, suggesting a non-visual source of the impairment. Scopolamine, mecamylamine and clonidine affected both P(hit) and P(fa); pilocarpine and idazoxan reduced P(hit) without affecting P(fa). Nicotine at 0.75 mg/kg decreased P(hit) in the first block of trials; at 0.08 mg/kg it increased P(hit) in the second block; no dose affected P(fa). RTs were increased by pilocarpine, scopolamine, mecamylamine and clonidine, but not by nicotine or idazoxan. The data suggest that drugs which reduce cholinergic or adrenergic tone (scopolamine, mecamylamine and clonidine) impair sustained attention by decreasing the detection of signals and by increasing the false alarm rate, whereas drugs which elevate cholinergic or adrenergic tone (pilocarpine, nicotine and idazoxan) decrease attention by impairing detection of signals without affecting the false alarm rate. In contrast, the GABA-facilitating drug chlordiazepoxide appeared to affect visual thresholds rather than attention. Received: 16 October 1996 /Final version: 16 May 1997     

Nicotine discrimination and self-administration in humans as a function of smoking status

Nicotine’s discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 μg/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 μg/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 μg/kg nicotine from placebo (≥ 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 μg/kg on the quantitative task and at 12 μg/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of “head rush”, which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use. Received: 1 October 1996/Final version: 28 January 1997     

Effects of central and peripheral nicotinic blockade on human nicotine discrimination

Nicotine produces interoceptive stimulus effects in humans, which may be critical in understanding tobacco use. It has not yet clearly been demonstrated that discrimination of nicotine, or any drug, in humans is due to its central effects. We compared effects of mecamylamine (10 mg PO), a central and peripheral nicotine antagonist, on nicotine discrimination with those of trimethaphan (10–40 μg/kg per min IV), a peripheral nicotine antagonist only, and placebo. Smokers (n = 6) were first trained to reliably discriminate 0 versus 20 μg/kg nicotine by nasal spray and then tested on generalization of this discrimination across a range of nicotine doses (0, 3, 6, 12, 20 μg/kg) following antagonist/placebo pretreatment. Nicotine self-administration was also assessed after generalization testing by having participants intermittently choose between nicotine versus placebo spray. Compared with responding following placebo pre-treatment, discrimination of the highest dose of nicotine was significantly attenuated following mecamylamine but not trimethaphan. Similar results were observed for some subjective responses to nicotine. Mecamylamine also tended to increase nicotine self-administration. Consistent with previous animal studies, these results suggest that discriminative stimulus effects of nicotine in humans are mediated at least in part by its central effects. Received: 15 April 1998/Final version: 23 July 1998     

Involvement of the prefrontal cortex but not the dorsal hippocampus in the attention-enhancing effects of nicotine in rats

Rationale Nicotine can enhance attentional performance in humans, a property that may be of therapeutic utility. Objectives To identify brain sites mediating nicotine-induced attentional enhancement. Methods Nicotine (0, 1, 2, 4 and 8 μg) was injected bilaterally into the dorsal hippocampus and the prelimbic area of the prefrontal cortex, brain sites implicated in cognitive functions, of rats performing the five-choice serial reaction time task (5-CSRTT). This rodent model of attention required the detection of light stimuli presented randomly in one of five locations during 30-min sessions. Systemically administered nicotine (0.1 and 0.2 mg/kg SC) was tested alongside local injections as a positive control. Results Nicotine (SC) enhanced response accuracy, reduced omission errors and shortened response latency. Nicotine injected into the dorsal hippocampus had no effect on any measure of performance except a slight decrease in latency in some animals at lower doses. By contrast, local injections of nicotine into the prefrontal cortex caused a dose-related increase in accuracy, the measure most closely reflecting stimulus detection and attention. Nicotine also increased omission errors selectively in the first 10 min of sessions and slightly reduced premature responding in the intertrial interval. No effects on response latency were observed. Conclusions The results implicate the prefrontal cortex, but not the dorsal hippocampus, in the attention-enhancing effects of nicotine. The targeting of nicotinic receptor subtypes expressed in the prefrontal cortex may be of particular benefit for the treatment of chronic disease states characterised by attentional dysfunction.     

An investigation into the effects of nicotine gum on short-term memory

Using a between-subjects 2 × 2 × 2 factorial design, 60 smokers and 60 non-smokers (equal number of males and females) performed a short-term memory task requiring delayed free recall of a visually presented supraspan word list. Using a double-blind procedure, half the subjects chewed nicotine gum and the other half chewed placebo gum prior to performing the memory task. Results support previous research findings which show that nicotine significantly improves short-term memory. Sex differences were also investigated, but findings showed no significant differences between male and female subjects. Methodological considerations are discussed and directions for future research are suggested. Received: 12 November 1997/Final version: 13 May 1998     

Treatment of neuroleptic-induced akathisia with nicotine patches

We administered 14 mg nicotine patches to 16 patients,all non-smokers, who displayed akathisia from antipsychotic drugs. On single-blind ratings, akathisia appeared significantly reduced on days when patients were wearing the patches as compared to the baseline day. These findings, if confirmed, may help to explain the high rates of tobacco use among psychotic patients, and may suggest avenues for the treatment of akathisia. Received: 5 March 1997 /Final version: 13 June 1997     

Nicotine improves delayed recognition in schizophrenic patients

Rationale Nicotine has been shown to enhance some aspects of memory, attention and cognition in normal subjects and in some patient populations such as Alzheimers and Parkinsons disease groups.Objectives Memory disorders are consistently observed in schizophrenic patients, so it is of interest to determine whether nicotine might improve memory performance in these patients.Methods Delayed recognition was assessed using yes/no recognition of visuospatial designs. Working memory was assessed in a delayed match-to-sample paradigm using unfamiliar faces. Nicotine (1.0 mg delivered via nasal spray) was administered to schizophrenic patients and normal volunteers prior to testing in the nicotine condition. Results were compared to a baseline condition in which no nicotine was given.Results On both tasks, normal volunteers performed better overall than schizophrenic patients. Significant improvement following nicotine administration was obtained only on the delayed recognition task and only for the subset of schizophrenic patients who were smokers. This improvement reflected a reduction in false alarm rates in the nicotine condition; hit rates were unaffected by nicotine.Conclusions These results suggest that nicotine enhances delayed recognition memory in schizophrenic patients who smoke, but that similar performance enhancement is not observed for working memory.     

Nicotine availability from Eclipse tobacco-heating cigarette

A cigarette which heats rather than burns tobacco (Premier) was introduced in 1988, but was unacceptable due to unpleasant taste and low nicotine intake. We examined availability of nicotine from a new version (Eclipse), in the same four subjects as our earlier Premier study. Average blood nicotine boosts of 23.7 and 17.8 ng/ml were obtained from smoking a first and second Eclipse. This substantially exceeds intake from Premier (boost 13 ng/ml) and that obtained by heavy smokers from conventional brands (boost 12–15 ng/ml). Eclipse (or similar product) may be the best option for averting Peto’s dire warnings of rising millions of annual smoking deaths in the 2020 s, and its potential for large-scale, long-term switching warrants further study. Received: 24 April 1998/Final version: 28 May 1998     

The nitric oxide synthesis inhibitor nitro-L-arginine (L-NNA) attenuates nicotine abstinence syndrome in the rat

Nitric oxide synthesis contributes to opiate tolerance and dependence. Nicotine dependence and abstinence syndrome in the rat appear to involve opiate mechanisms. Therefore, it was postulated that nitric oxide synthase (NOS) activity might be essential for the expression of nicotine abstinence syndrome. Twenty-one rats were rendered dependent by SC infusion of 9 mg/kg per day nicotine tartrate via Alzet osmotic minipump. Rats were pretreated SC with vehicle alone, or with 18 or 30 mg/kg of the NOS inhibitor L-NNA (nitro-L-arginine). Thirty minutes later, rats were challenged by 1 mg/kg of the nicotinic antagonist mecamylamine SC and observed for 30 additional minutes. Rats pretreated with vehicle displayed a total of 68.7 ± 8.0 mecamylamine-precipitated abstinence signs (mean ± SEM), while those receiving 18 or 30 mg/kg L-NNA had 12.7 ± 2.0 and 5.1 ± 1.7 signs, respectively. All three groups differed significantly from one another according to Dunn’s post-hoc procedure. Rats pretreated with L-NNA combined with an excess of the NOS substrate L-arginine had significantly more mecamylamine-precipitated abstinence signs than rats receiving L-NNA combined with D-arginine. Also, D-NNA, which does not selectively bind to NOS, was significantly less effective than L-NNA in preventing mecamylamine-precipitated abstinence syndrome. Additional studies determined the effect of L-NNA on spontaneous nicotine abstinence syndrome. Rats were assessed for abstinence signs at 17 and 20 h after termination of nicotine infusion. They received injections of 9, 18, or 30 mg/kg L-NNA SC or vehicle alone immediately before the 20-h observation; all rats were observed for 30 min. Signs at 20 h (post-injection) as a percentage of signs at 17 h (pre-injection) declined significantly as a function of L-NNA dose. Once again, this effect was attenuated significantly more by co-administration of L-arginine than by D-arginine. The overall pattern of results suggests that nitric oxide synthesis is critical to the expression of nicotine abstinence syndrome. Received: 20 January 1998/Final version: 8 April 1998     

Effects of transderman nicotine on mood and sleep in nonsmoking major depresssed patients

The role of nicotine as an indirect cholinergic agent in sleep has been studied in normal subjects. There are no studies of its effects on sleep in depressed patients. Nicotine transdermal patches (17.5 mg), were studied in eight depressed patients (DSM-III-R) and eight normal volunteers. Subjects wore placebo and nicotine patches for 24 h. Depressed patients showed increased REM sleep without changes in other sleep variables. They also showed a short term improvement of mood. Normal volunteers had sleep fragmentation, and reduction of REM sleep time. No major side effects were reported in either group.     

The effects of nicotine on the attentional modification of the acoustic startle response in nonsmokers

RATIONALE AND OBJECTIVE: Research on nicotine and attention has mainly utilized samples of deprived smokers and tasks requiring volitional responses, raising the question of whether nicotine improves attention or simply alleviates withdrawal or improves motor speed. This study used the startle eyeblink reflex to assess nicotine effects on auditory attention in nonsmokers. MATERIALS AND METHODS: Sixty-seven healthy young adult nonsmokers completed a tone discrimination task. Acoustic startle probes were presented 60, 120, 240, or 4,500 ms after the onset of two-thirds of the tones and during intertrial intervals. Attention was assessed via (1) short-lead prepulse inhibition (PPI) of startle, a measure of early filtering; (2) long-lead prepulse facilitation (PPF) of startle, a measure of sustained processing; and (3) the modification of PPI and PPF by focused attention. Participants completed two laboratory sessions, once while wearing a 7-mg transdermal nicotine patch and once while wearing a placebo patch. Patches were administered in a double-blind procedure. RESULTS: Nicotine increased overall PPI, eta2(p)=0.09. Attention increased long-lead PPF, eta2(p)=0.25, but not short-lead PPI. Nicotine did not reliably enhance early or late controlled attentional processing in the sample overall. However, correlational analyses demonstrated that nicotine most improved attentional modification of short-lead PPI among participants with the weakest early attentional processing under placebo conditions. CONCLUSIONS: Nicotine enhanced early attentional filtering in general, and the effects of nicotine on early focused attention were dependent upon individual differences in placebo levels of attentional processing. The present data suggest that the effects of nicotine on attention extend beyond the alleviation of withdrawal and simple motor speeding.     

Influence of nicotine on simulator flight performance in non-smokers

In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior to each test, subjects received either nicotine polacrilex 2 mg or placebo gum. As expected, overall performance was significantly better after nicotine, compared to placebo (P < 0.01). Post-hoc analysis of individual flight tasks showed that nicotine improved scores on approach to landing, a task which appears to require sustained attention. We conclude that nicotine may improve late-day flight performance in non-smoking aviators. Received: 15 September 1997/Final version: 11 March 1998