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1.
Effects of central and peripheral nicotinic blockade on human nicotine discrimination 总被引:2,自引:1,他引:1
Perkins KA Sanders M Fonte C Wilson AS White W Stiller R McNamara D 《Psychopharmacology》1999,142(2):158-164
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 相似文献
2.
Acute subjective and physiological effects were examined to provide information relevant to abuse liability of new nicotine
delivery systems. Subjects (n = 12) were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from nicotine-containing cigarettes (0.1 mg
per puff), 0, 1, 2 or 4 nasal sprays (0.5 mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013 mg
nicotine per inhalation) in a within-subject single blinded design. While smokers clearly liked cigarette puffs, there was
much less evidence of liking produced by either nasal spray or vapor inhaler; only modest elevations on a measure of good
drug effects were observed. The novel delivery products engendered unpleasant effects of burning throat and nose, watery eyes,
runny nose, coughing and sneezing that might be expected to limit abuse liability. Nicotine plasma level and heart rate increase
was dose-related for cigarettes and nasal spray but not for vapor inhaler, indicating limited nicotine delivery with the latter
device. Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially
lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products.
Received: 28 May 1996 / Final version: 25 October 1996 相似文献
3.
These studies aim to characterize the discriminative stimulus effects of nicotine in two inbred strains of mice that differ
in many pharmacological responses, and to investigate the feasibility of IV self-administration studies with nicotine in one
of the strains. For discrimination studies, three groups of C57BL/6 and one group of DBA/2 mice were trained in a two-lever
operant conditioning paradigm with a tandem VI-30″ FR-10 schedule of food reinforcement. After 40 training sessions, accuracy
reached 57.5, 77.5 and 90.0% in C57BL/6 mice trained with (–)-nicotine (SC) in doses of 0.4, 0.8 and 1.6 mg/kg, respectively
(n = 8). DBA/2 mice trained with 0.8 mg/kg nicotine attained similar (73.3%) accuracy (n = 9). Results from extinction tests showed that all groups of mice yielded orderly dose-response curves for nicotine (0.03–1.6
mg/kg), but stimulus control remained notably weaker for the mice trained with 0.4 mg/kg nicotine than for any other group.
Overall rates of responding in the undrugged state were lower for DBA/2 than for C57BL/6 mice; DBA/2 mice were also slightly
less sensitive than C57BL/6 mice to the response rate-reducing effect of nicotine. The nicotine antagonist mecamylamine (1.5 mg/kg
SC) blocked the discriminative stimulus effect of the training dose of nicotine in all groups. The results of the IV self-administration
study suggest that nicotine (0.1 mg/kg) can serve as a positive reinforcer in drug–naive C57BL/6J mice (n = 13). Behaviour maintained by 0.1 mg/kg nicotine injections was significantly greater than behaviour maintained by vehicle
injections, and it was maintained under an intermittent schedule of reinforcement (FR4). The methods described provide possible
approaches for genetic analyses of strain differences in sensitivity to the discriminative and reinforcing stimulus properties
of nicotine.
Received: 11 April 1998/Final version: 28 June 1998 相似文献
4.
Dorothy K. Hatsukami Kelli Skoog Marguerite Huber John Hughes 《Psychopharmacology》1991,104(4):496-504
This study examined and compared withdrawal signs and symptoms from cessation of 0, 2 and 4 mg nicotine gum. In addition, a comparison was made between nicotine gum versus cigarette withdrawal symptoms. Smokers first underwent cigarette deprivation for 4 days and then were randomly assigned to 0 (N=16), 2 (N=25), and 4 (N=21) mg gum. They were asked to chew the gum for 1 month and then to undergo a 4-day nicotine gum deprivation period. The results showed a number of significant changes occurring after deprivation from 4 mg gum, one change from 2 mg gum, and no changes from 0 mg gum. There were no significant differences in severity of withdrawal among the various doses of nicotine gum. There were more severe symptoms of withdrawal from cigarette as opposed to 4 mg nicotine gum deprivation. 相似文献
5.
Guthrie SK Zubieta JK Ohl L Ni L Koeppe RA Minoshima S Domino EF 《European journal of clinical pharmacology》1999,55(9):639-643
Background and objectives: Arterial (A) and venous (V) plasma nicotine and cotinine concentrations were measured after nasal nicotine spray in tobacco
smokers of both genders. The hypothesis for this research was that a greater A/V difference in plasma nicotine would be present
in males than females because males have greater skeletal muscle mass to bind nicotine.
Subjects and methods: Nine male and nine female healthy adult smokers were studied. They all abstained from use of tobacco overnight for 10 h
or more prior to the study. Nicotine nasal spray was given in doses of 1–2.5 mg total, with half in each nostril while the
subject was supine. Both A and V blood samples were obtained prior to and 3, 6, 10, 15, 20, and 30 min post-nasal nicotine
spray.
Results and conclusions: Nasal nicotine administration produced greater A than V plasma levels. There were no gender differences in A/V nicotine
concentrations, disproving the above hypothesis, suggesting that other physiochemical factors besides skeletal muscle mass
must be involved. Heart rate increases correlated well with arterial plasma nicotine levels (r=0.77). Males had less variance than females in the expected increase in arterial plasma nicotine concentrations with increased
number of nasal sprays. Although there was considerable overlap, mean A cotinine concentrations were consistently slightly
larger than V concentrations.
Received: 15 February 1999 / Accepted in revised form: 17 August 1999 相似文献
6.
Schneider NG Terrace S Koury MA Patel S Vaghaiwalla B Pendergrass R Olmstead RE Cortner C 《Psychopharmacology》2005,182(4):545-550
Rationale Misuse or dislike of nicotine replacement treatments (NRTs) undermines their effectiveness. Brief testing among NRTs could
allow tailoring by preference to improve outcome.
Objective To test initial reactions/preferences to NRTs in a single session crossover design with guided use.
Methods Smokers were offered two doses of three NRTs: gum (2 and 4 mg), inhaler, and nasal spray (NNS) in a 5-h test with proper use
enforced. Subjects rated each NRT and ranked among NRTs on use variables and preferences.
Results Gum was ranked over inhaler and NNS for “ease of use,” “safety” and “prefer in public.” Four-milligram gum was rated higher
than 2 mg on several variables. With experience, “ease of use” and “liking” improved for gum. Both inhaler and NNS ranked
low on considering “use >3 months” vs gum. Dislike of NRT was reflected in refusal of second doses. For those testing all
doses (n=9), inhaler ranked last on “relief of withdrawal,” “choose under stress,” and “choice to help quit.” Craving and withdrawal
were relieved over time with any NRT use.
Conclusions Sampling of treatments can identify reactions key to initial compliance with these NRTs. 相似文献
7.
The nitric oxide synthesis inhibitor nitro-L-arginine (L-NNA) attenuates nicotine abstinence syndrome in the rat 总被引:1,自引:1,他引:0
D. H. Malin J. Ronald Lake Merle Shenoi Timothy P. Upchurch Shun C. Johnson Will E. Schweinle Chris D. Cadle 《Psychopharmacology》1998,140(3):371-377
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 相似文献
8.
Nicotine gum and transdermal nicotine have been shown to relieve withdrawal and double success rates over placebo in trials of smoking cessation. This study tested whether combining the two methods would relieve withdrawal more effectively compared to either treatment alone. Twenty-eight smokers served as their own controls in each of four conditions: active gum + active patch (double active), active gum + placebo patch (gum only active), placebo gum + active patch (patch active) and placebo gum+placebo patch (double placebo). This double placebo design controls sensory, psychological and ritual variables associated with each drug form. Withdrawal symptoms were rated four times daily for 3 days in each condition. Total baseline (smoking) withdrawal scores using visual analogue scales (VAS) averaged 101.1. During cessation, total withdrawal increased to 187.0 for the double placebo condition, 142.2 for the active gum/placebo patch treatment and 128.3 for the active patch/placebo gum treatment. The double active condition equalled smoking with score 99.2. All pairwise comparisons were significant (P<0.001) except between the two single active conditions and between smoking versus the double active condition. Significant time-of-day effects by treatment on withdrawal were observed for the double placebo condition (P<0.05) with less withdrawal in the morning. The findings suggest: 1) combining nicotine gum with transdermal nicotine may be superior to either treatment alone, 2) more symptoms may be nicotine specific (relieved by replacement) than previously thought. 相似文献
9.
Behavioral manifestations of the nicotine abstinence syndrome in the rat: peripheral versus central mechanisms 总被引:8,自引:8,他引:0
B. E. Hildebrand G. G. Nomikos C. Bondjers M. Nisell T. H. Svensson 《Psychopharmacology》1997,129(4):348-356
The nicotine abstinence syndrome was studied in the rat utilizing a modified rating scale of the opiate abstinence syndrome.
Rats were infused with 10.27 mg/kg per day nicotine hydrogen tartrate for 7 days via subcutaneous minipumps. The behavior
of each animal was observed before, during and after termination of the nicotine infusion. The abstinence signs in the withdrawal
sessions included gasps, genital licks, ptosis, shakes, teeth chatter, yawns and changes in locomotor activity. Abstinence
was induced through surgical removal of the pump or through administration of a nicotinic receptor antagonist, acting either
centrally and peripherally (mecamylamine 1 mg/kg SC) or peripherally only (chlorisondamine 1 mg/kg SC). Statistical evaluation
revealed a significant increase in overall abstinence signs both at 16 (P < 0.05) and 40 h (P < 0.01) after termination of the nicotine infusion, as compared to the number of signs in the nicotine treated animals’ baseline
sessions and to the number of signs in control animals (P < 0.05). There was also a significant reduction in locomotor activity during both withdrawal sessions. Animals injected with
mecamylamine or chlorisondamine displayed a larger increase in the abstinence score (P < 0.001) than the spontaneously abstinent animals. Acute administration of different doses of nicotine or of the peripherally
acting nicotinic receptor agonist tetramethylammonium (0.8 mg/kg SC) reversed the behavioral nicotine abstinence syndrome.
Our results show that a nicotine abstinence syndrome can be elicited in rats on a chronic nicotine regimen either by acute
withdrawal of nicotine or by the administration of nicotinic receptor antagonists and that peripheral nicotinic receptors
may contribute significantly to the overall withdrawal reaction.
Received: 21 March 1996/Final version: 30 September 1996 相似文献
10.
Subjective and cardiovascular effects of intravenous nicotine in smokers and non-smokers 总被引:4,自引:4,他引:0
Rebeca Soria June M. Stapleton Stephen F. Gilson Angela Sampson-Cone Jack E. Henningfield E. D. London 《Psychopharmacology》1996,128(3):221-226
The present study assessed the subjective and cardiovascular effects of intravenous nicotine in smokers and nonsmokers. Nonsmokers
(n = 5) and smokers (n = 5) were administered a single dose of nicotine (0.75 or 1.5 mg) or saline on each of 3 days. The nicotine doses were given
in ascending order in a double-blind fashion. Although smokers and nonsmokers manifested significant increases in systolic
and diastolic blood pressure and heart rate 1 min after administration of all active test doses, the difference between peak
heart rate and that measured at later times was greater in nonsmokers than in smokers. Nonsmokers and smokers also differed
in subjective self-reports. In response to items on visual analogue scales indicative of positive effects (e.g., “good effects,”“like
drug,”“use again,” and “feel energetic”), smokers but not nonsmokers reported high scores (> 40) after nicotine injection.
In addition, responses on the MBG and LSD subscales of the Addiction Research Center Inventory indicated that smokers experienced
positive subjective effects after the test doses, whereas nonsmokers experienced disorientation. The fact that intravenous
nicotine was not associated with positive subjective effects in nonsmokers indicates that repeated exposure is required to
establish positive reinforcing effects of nicotine.
Received: 11 August 1995 /Final version: 30 May 1996 相似文献
11.
Endogenous opioid peptides have been implicated in the reinforcement of smoking and opioid antagonists have been examined
to determine their role in smoking behavior. To date, the relationship between smoking behavior and chronic opiate antagonist
administration during ad libitum smoking has not been investigated. The purpose of this study was to examine the relationships
between naltrexone, an opiate antagonist administered orally, and smoking behavior and mood states during ad libitum smoking.
A repeated measures experimental design was used. Normal adult male and female volunteers, admitted to the Clinical Research
Center, were randomly assigned to naltrexone-treated (n = 22) or placebo-control (n = 21) groups in a double-blind manner. Day 1 was considered acclimation to the unit and day 2 was baseline, or pre-drug administration.
On days 3, 4, and 5, subjects received 50 mg naltrexone or a placebo at 0700 and 1600 hours. Plasma nicotine and expired air
carbon monoxide levels were measured daily at 1900 hours. Number of cigarettes smoked, mood states, withdrawal symptomatology
and self-reported satisfaction with smoking were also quantified daily. Results indicated that plasma nicotine levels (P = 0.005), number of cigarettes smoked daily (P = 0.003) and self-reported satisfaction with smoking (P = 0.043) were significantly lower among those treated with naltrexone, compared to the placebo-control group. Expired air
carbon monoxide levels did not differ between the two groups. In addition, mood states and withdrawal symptoms did not differ
between groups. These findings suggest that endogenous opioid peptides influence specific smoking behavior variables.
Received: 7 November 1997/ Final version: 7 April 1998 相似文献
12.
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 相似文献
13.
Immunization of rats reduces nicotine distribution to brain 总被引:3,自引:3,他引:0
Yoko Hieda Dan E. Keyler John T. VanDeVoort R. Sam Niedbala Donna E. Raphael Cathy A. Ross P. R. Pentel 《Psychopharmacology》1999,143(2):150-157
The effect of active immunization against nicotine on the initial distribution of nicotine to brain was studied in anesthetized
rats. Animals received nicotine 0.03 mg/kg nicotine (equivalent to the nicotine dose absorbed by a human smoking two cigarettes)
as a rapid injection in the jugular vein. In control animals, the arterial serum nicotine concentration initially exceeded
the venous concentration 4.6-fold, similar to the initial arteriovenous difference produced by cigarette smoking in humans.
Animals immunized with the nicotine analog CMUNic maintained this arteriovenous gradient, but with both arterial and venous
nicotine concentrations several times higher than in controls. The arterial nicotine concentration was higher in immunized
animals even at the first (7.5 s) sampling time. The brain nicotine concentration at 3 min was 36% lower in the immunized
animals. The time course of nicotine distribution to brain was studied in a second group of animals. Brain nicotine concentration
was reduced in rats immunized with CMUNic over the entire 6-min sampling period immediately following nicotine dosing (mean
reduction 38%). A reduction was found at the earliest sampling time (30 s) and was maximal at 1 min (48%). Nicotine protein
binding in serum was markedly increased in animals immunized with CMUNic compared to controls (91.2 versus 10.9%), and the
unbound nicotine concentration in serum was lower (10.0 versus 13.4 ng/ml). The reduction in brain nicotine concentration
correlated with antibody affinity for nicotine, and the percentage of nicotine bound in serum. These data demonstrate that
nicotine-specific antibodies produced by active immunization rapidly bind nicotine in arterial blood, reduce the unbound nicotine
concentration, and reduce the early distribution of nicotine to brain. Effects were observed using a clinically relevant nicotine
dose and route of administration. These data suggest that the use of immunization to modify the behavioral effects of nicotine
may be possible.
Received: 6 July 1998/Final version: 24 August 1998 相似文献
14.
E. D. Levin C. Keith Conners Donna Silva Sean C. Hinton Warren H. Meck John March Jed E. Rose 《Psychopharmacology》1998,140(2):135-141
Nicotine has been shown to improve attentiveness in smokers and attenuate attentional deficits in Alzheimer’s disease patients,
schizophrenics and adults with attention-deficit/hyperactivity disorder (ADHD). The current study was conducted to determine
whether nicotine administered via transdermal patches would improve attentiveness in non-smoking adults without attentional
deficits. The subjects underwent the nicotine and placebo exposure in a counterbalanced double-blind manner. Measures of treatment
effect included the Profile of Mood States (POMS), Conners’ computerized Continuous Performance Test (CPT) of attentiveness
and a computerized interval-timing task. The subjects were administered a 7 mg/day nicotine transdermal patch for 4.5 h during
a morning session. Nicotine significantly increased self-perceived vigor as measured by the POMS test. On the CPT, nicotine
significantly decreased the number of errors of omission without causing increases in either errors of commission or correct
hit reaction time. Nicotine also significantly decreased the variance of hit reaction time and the composite measure of attentiveness.
This study shows that, in addition to reducing attentional impairment, nicotine administered via transdermal patches can improve
attentiveness in normal adult nonsmokers.
Received: 11 June 1997/Final version: 13 March 1998 相似文献
15.
Nicotine discrimination and self-administration in humans as a function of smoking status 总被引:2,自引:2,他引:0
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 相似文献
16.
A further study of FTC yield and nicotine absorption in smokers 总被引:1,自引:1,他引:0
G. D. Byrd R. A. Davis W. S. Caldwell J. H. Robinson J. D. deBethizy 《Psychopharmacology》1998,139(4):291-299
The relationship between nicotine yield as determined by the FTC method and nicotine absorption was examined in 72 smokers
in a more rigorous repetition of a previous study of 33 smokers. For this study, 113 smokers evenly distributed across four
FTC “tar” yield ranges were recruited; only 72 demonstrated reasonable compliance with the study criteria with regard to sample
collections and cigarette brand style consistency. Subjects recorded the number of cigarettes smoked daily and collected a
24-h urine sample and a saliva sample on 3 consecutive days. Nicotine absorption was determined by monitoring urinary excretion
of nicotine and its metabolites. In addition, saliva samples were monitored for cotinine using radioimmunoassay (RIA). The
correlation of the relationship for nicotine absorbed per cigarette was positive and significant (r = 0.31, P = 0.008) but weaker than in the previous study. Only smokers in the highest yield range showed any statistical difference
from smokers in the lower ranges. Our results suggest that FTC nicotine yield is weakly related to nicotine absorption and
that smoker-controlled factors exert a great influence on the amount of nicotine absorbed by smokers. Compensation is substantial
but incomplete for the minority (by market share) of smokers at the low end of the yield scale. It is uncertain how well any
alternative set of machine parameters would predict nicotine absorption for the majority of smokers, even if it were more
predictive for the small number of smokers at the lower yield part of the range.
Received: 5 March 1997/Final version: 19 December 1997 相似文献
17.
M. S. Mumenthaler Joy L. Taylor Ruth O’Hara Jerome A. Yesavage 《Psychopharmacology》1998,140(1):38-41
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 相似文献
18.
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 相似文献
19.
There were two experiments on abstinence from smokeless tobacco. The purpose of the first experiment was to determine abstinence effects from smokeless tobacco. The purpose of the second experiment was to examine the effects of different doses of nicotine gum on smokeless tobacco abstinence effects. The subjects were male Copenhagen smokeless tobacco users who underwent 3 days of baseline measurement while continuing to use smokeless tobacco ad libitum, and 5 days of the experimental condition. In the first experiment, the subjects were assigned randomly to one of two groups and compared: continuous smokeless tobacco users (n=10), and deprivation plus no nicotine gum (n=10). In the second experiment, subjects were assigned randomly and in a double-blind fashion to one of three groups and compared: (1) deprivation plus 0 mg nicotine gum (n=20); (2) deprivation plus 2 mg nicotine gum (n=20); and (3) deprivation plus 4 mg nicotine gum (n=20). The first experiment showed significant increases upon abstinence for the following variables: (1) craving; (2) difficulty concentrating; (3) restlessness; (4) excessive hunger; (5) eating; (6) reaction time; (7) variability of reaction time and (8) total withdrawal scores for both the self-rated and the observer-rated forms. The second experiment showed that nicotine gum failed to significantly reduce smokeless tobacco abstinence effects, although those with high cotinine levels may receive some benefit from nicotine gum.Sponsored by the National Institute on Drug Abuse Research Grant No. DA05013 相似文献
20.
Experimentally naive male, Sprague-Dawley rats maintained at 85% of their original body weight were trained to touch a retractable lever that was presented on a random interval 48-s schedule. The lever retracted when touched or after 15 s had elapsed, and one 45 mg food pellet was delivered simultaneously with lever retraction or after an 8-s delay. Rats received ten daily sessions each consisting of ten lever presentations. Nicotine (0.25–0.8 mg/kg SC) administration, either 15 min prior to (pre-session) or immediately after (post-session) the daily autoshaping sessions, caused a significant dose-related impairment of acquisition with the post-session injections having the greater effect. Low doses of nicotine (0.025–0.1 mg/kg SC) had little effect on acquisition when injected pre-session or post-session. Injections of 0.45 mg/kg nicotine either immediately (t=0) or at +5 min after the daily sessions impaired acquisition of the lever-touch response. Nicotine injected at +15, +30, +60, or +120 min had no effect on acquisition. A single intraventricular injection of the ganglionic blocker chlorisondamine (5 g) 2 weeks prior to autoshaping blocked the impairment produced by 0.45 mg/kg nicotine. Post-session injections of nicotine did not alter the lever-touch behavior of well-trained animals, but suppressed responding in animals that were partially trained. Thus, nicotine-induced impairment of the autoshaped lever-touch response is dose dependent, centrally mediated, occurs within 5 min of a SC injection, and may interfere with post-training consolidation processes.
Offprint requests to: E.T. Iwamoto 相似文献