Selective effects of nicotine on attentional processes

Rationale: It is now well established from electrophysiological and behavioural evidence that nicotine has effects on information processing. The results are usually explained either by a primary effect of nicotine or by a reversal effect of a nicotine-induced, abstinence deficit. In addition, there is dispute about the cognitive processes underlying the changes in performance. Methods: This study has approached the first question by using the nicotine patch, in order to administer nicotine chronically. In addition, we examined the effects of nicotine on attention with a selection of tests which assessed the intensity and selectivity features of attention, using the Random Letter Generation test, the Flexibility of Attention test and the Stroop test. Results: Nicotine enhanced the speed of number generation and the speed of processing in both the control and interference conditions of the Stroop test. There were no effects on attentional switching of the Flexibility of Attention test. Conclusion: The results are consistent with the hypothesis that nicotine mainly improves the intensity feature of attention, rather than the selectivity feature. Received: 8 February 1999 / Final version: 28 April 1999     

Alcohol-Related Words of Positive Affect are More Accessible in Social Drinkers' Memory Than are Other Words When Sip-Primed by Alcohol

Alcohol-related consequences of consumption with positive affect are claimed to be more accessible in memory than are negative, and to a limited extent this has been demonstrated with recall paradigms. This hypothesis is tested with a more robust recognition paradigm, the automated Stroop. A 3-factor mixed design was used: between subjects factor was Prime (soft or alcoholic drink); two within subjects factors were related to the Stroop word stimuli, Affect (positive or negative) and Alcohol-relatedness (related or unrelated). Sixty paid, volunteer, social drinkers took part. Binary colour choice RTs were measured and Stroop Interference RTs were derived in the standard way. Only correct RTs were analysed. Using a 2×2×2 ANOVA, a significant 3-way interaction was found (p=0.029). Words depicting positive consequences of alcohol consumption had significantly higher interference scores than did words depicting negative in the group primed with alcohol drink sips but not in the group primed with soft drink sips.     

Classical conditioning in humans: nicotine as CS and alcohol as US

Animal studies suggest that drug effects can act as conditioned stimuli for various unconditioned stimuli including the effects of other drugs. The current study investigated drug-drug conditioning in human subjects. Sixteen subjects were given subcutaneous injections of either nicotine or saline before consumption of an alcoholic or soft drink in each of eight sessions. Across sessions the content of the injections was established as a reliable predictor of the alcoholic content of the drink. Physiological, subjective, and behavioural responses to the injections were used as indices of conditioning. Skin conductance measures obtained following the injections changed across trials in a way consistent with a conditioned response though patterns of change on cardiac inter-beat interval were less clear. However, neither behavioural nor subjective measures showed conditioning effects. In view of the number of variables studied the evidence for the development of conditioned responding on physiological measures must be suspected of being a type I error and is in need of replication. Subjects' reports revealed that nicotine and saline injections were difficult to discriminate. This would have weakened conditioning effects. Suggestions are made for improvements in the design of future studies of drug-drug conditioning in human subjects.     

A double-blind placebo controlled experimental study of nicotine: I—effects on incentive motivation

Rationale Brain reward pathways implicated in addiction appear to be less reactive in regular drug users; behavioural manifestations may include decreased sensitivity to natural reinforcers.Objectives This study aimed to replicate earlier findings of abstinence-associated incentive motivation deficits in smokers and to determine whether these can be reversed with nicotine in the form of lozenge.Methods One hundred forty-five smokers were each tested twice, once after receiving nicotine, and once after receiving placebo lozenge in counterbalanced order. Participants completed various tests of incentive motivational functioning: a measure of subjective enjoyment, the Snaith–Hamilton pleasure scale (SHAPS); a simple card sorting task, the card arranging reward responsivity objective test (CARROT) with and without financial incentive; the modified emotional Stroop test; a cue-reactivity task; and a novel reaction time task to explore effects of signals of reward, the incentive motivational enhancement of response speed task.Results Compared with performance during abstinence (placebo condition), nicotine was associated with: higher self-reported pleasure expectations on the SHAPS; enhanced responsiveness to financial reward on the CARROT in smokers who smoked 15 or more cigarettes a day; and greater interference from appetitive words on the Stroop task.Conclusions These results are generally consistent with contemporary neurobiological theories of addiction and suggest that short-term smoking abstinence is associated with impaired reward motivation which can be reversed with nicotine.     

Mecamylamine reduces some EEG effects of nicotine chewing gum in humans

Spontaneous EEG was recorded in nine cigarette smokers who had been abstinent from tobacco for 12 hr. Subjects were treated with a capsule containing either centrally acting nicotine blocker, mecamylamine (10 mg), or placebo. At each of three 60-min intervals after the capsule was ingested, the subjects chewed two pieces of gum containing a total of 0, 4 or 8 mg of nicotine. Nicotine and mecamylamine dose combinations were randomized across subjects. Two three-minute periods of spontaneous EEG were recorded before the capsule and before and after gum chewing from bipolar electrode montages at the following positions: Cz-T5, Cz-T6, Cz-F7 and Cz-F8. During one period the subjects relaxed with eyes closed, in the other period they performed a math task with eyes open. When the drugs were given individually, mecamylamine decreased beta power and nicotine gum (4 and 8 mg) increased alpha frequency. Mecamylamine pretreatment prevented the increase in alpha frequency caused by the 4 mg gum dose but not the 8 mg dose. Alpha power was increased by the 8 mg gum dose and that increase was prevented by mecamylamine. Self-reported ratings of the "strength" of the gum were significantly diminished by mecamylamine pretreatment. The data are consistent with the results of earlier studies which indicate that the effects of tobacco administration and withdrawal are mediated by central actions of nicotine.     

The smoking Stroop and delay discounting in smokers: effects of environmental smoking cues

We investigated the effects of exposure to environmental smoking-related cues (holding a lit cigarette in an environment previously associated with smoking) on cigarette craving, colour naming of smoking-related words in a modified Stroop task, and on the delay discounting of hypothetical rewards, in daily cigarette smokers (N = 30). Compared to exposure to neutral cues, exposure to smoking-related cues was associated with increased cigarette craving and slower colour naming of smoking-related compared to matched control words. However, smoking cues had no effect on delay discounting. These results suggest that smoking cues increase craving and the ability of smoking-related words to grab the attention, but do not influence impulsive decision-making. Theoretical and clinical implications are discussed.     

美沙酮维持治疗海洛因成瘾者的冲动性与抑制控制研究

目的：以海洛因成瘾戒断康复组、接受美沙酮维持治疗的海洛因成瘾组以及无过往吸毒史的对照组为研究对象,比较3组被试的冲动性水平以及抑制控制功能。方法：采用修订后的巴瑞特冲动性量表第11版（BIS-11）和经典色词Stroop任务比较3组被试在冲动性水平和抑制控制功能上的差异。结果：海洛因成瘾戒断康复组和接受美沙酮维持治疗的海洛因成瘾组在巴瑞特冲动性量表总分以及3个维度上的得分均显著高于对照组,在经典的色词Stroop任务中,接受美沙酮维持治疗的海洛因成瘾组的Stroop干扰效应量显著高于对照组,海洛因成瘾戒断康复组的Stroop干扰效应量和对照组没有显著差异。结论：海洛因成瘾戒断康复组和接受美沙酮维持治疗的海洛因成瘾组具有更高的冲动性并且接受美沙酮维持治疗的海洛因成瘾组的抑制控制功能受损。     

Nasal nicotine spray: a rapid nicotine delivery system

Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed.     

Improved incidental memory with nicotine after semantic processing, but not after phonological processing

RATIONALE: A number of lines of evidence suggest that a nicotinic cholinergic system is mediating attentional processing. However, the evidence is less clear for a nicotinic system being involved in mnemonic processing. OBJECTIVES: The present study investigated the effects of nicotine on memory using a depth of processing paradigm. METHODS: A double-blind design was used with participants (n = 40) smoking either a nicotine containing cigarette (n = 20) and a denicotinized cigarette (n = 20). After smoking, each set of these participants was further subdivided into two groups (n = 10 for each). One group were presented with a series of trials each beginning with the presentation of a "decision word" which they had to say whether it represented something which was living or non-living (semantic-orienting). The second group had to say whether the word had one syllable or two syllables (phonological or non-semantic orienting condition). This decision was followed by a word in coloured ink whose colour participants were required to name as quickly as possible. On completion of the whole task the participants were given an unexpected free recall test. RESULTS: The nicotine-containing cigarette reduced the latencies for decision-making and colour naming in comparison with the denicotinized cigarette. The free recall test showed that nicotine-containing cigarette increased the number of words remembered, but only for the semantic-orienting condition and not the non-semantic condition. CONCLUSIONS: There is a nicotinic cholinergic system that mediates effortful processing. It can be deployed for attentional processing, including the associative processing required for memory encoding.     

Personality related effects of nicotine, mode of application, and expectancies on performance, emotional states, and desire for smoking

 Three separate factors relevant to nicotine effects have been investigated in this experiment in combination: the experimentally induced expectation about receiving a sham or a nicotine cigarette, the mode of application of nicotine by a tablet, by a cigarette or not at all, while the belief of receiving the nicotine via smoking was held constant in each condition (by nicotine or sham smoking), and the personality factors of extraversion or neuroticism, respectively. Ninety-six healthy female student smokers were tested in a 2 × 3 × 2 factorial group comparison design with respect to critical flicker fusion and reaction time performance as well as to self-ratings on emotional and cortical arousal and ratings on desire for further cigarettes (satisfaction from smoking a single cigarette containing either 0.8 mg nicotine or a sham cigarette). In each case, a tablet containing either nicotine or placebo was administered together with the cigarette. The results showed that performance is sensitive to interaction effects of instruction and mode of application. The instruction of sham or nicotine assignment when applied with a congruent treatment (sham with a sham cigarette, or nicotine with a nicotine cigarette) both increased performance, while groups with discordant information showed worse performance. The administration of nicotine by tablets or by smoking differs considerably, nicotine cigarettes causing a stronger increase in emotional arousal, tablets rather a decrease or no effect, while the true placebo condition increases arousal due to deprivation effects. This leads to an enhancement of the nicotine effect with real smoking and to reactive increase of effort when sham smoking. The instruction affects alertness, the nicotine illusion leading to a lower reduction in subjective reports of alertness and concentration than that observed with the sham instruction. Neurotic subjects become more anxious and tense with nicotine cigarettes than stable subjects. This effect is less pronounced or even reversed with tablets. No interactions with instructions are observed with neuroticism. Extraverts tend to show a decrease in performance but an increase in alertness with the instruction of receiving nicotine as opposed to the sham expectation, whereas introverts behave the opposite way. Subjective ratings on arousal seem to follow the law of transmarginal inhibition, with extraverts being pushed from low arousal to high and introverts vice versa by the mere expectation. Received: 11 February 1997/Final version: 30 June 1997     

Nicotine abstinence produces content-specific stroop interference

Adult, male smokers were randomly assigned to be nicotine abstinent for 12 h (n=10) or to smoke normally for the same period of time (n=10). Performance on a modified version of the Stroop (1935) color-naming task, where subjects named the color of ink in which each of a series of words was written, showed that abstinent smokers took significantly longer to color-name words related to cigarette smoking (e.g., Lighter) than to color-name neutral control words (e.g., Pennant). Non-abstinent smokers showed a significant difference in the opposite direction. These results suggest that nicotine abstinence decreases the ability to ignore the meaning of smoking-related information. This finding supports the hypothesis that abstinence produces a content-specific shift in attentional focus. The present pattern of results cannot be explained by a general decrease in cognitive function due to nicotine abstinence.     

Patterns of facilitation of memory by nicotine

A single oral dose of 1.5mg of nicotine was administered to healthy young normal males in a placebo-controlled double-blind study. The nicotine produced a significant improvement in the number of words recalled from a 32 item list. An examination of the individual serial position curves showed that most subjects were recalling either predominantly from the first half of the list or predominantly from the second half of the list. Examination of these groups separately showed that nicotine improved recall for the part of the list that was being recalled better in the placebo condition. These results are consistent with the hypothesis that nicotine was supplying additional processing resources and that deployment of these is under the strategic control of the subject.     

The separate and combined effects of scopolamine and nicotine on human information processing

Previous work in this and another laboratory has shown that nicotine tablets improve the performance of a rapid information processing task and reduce the Stroop effect, whereas scopolamine has the opposite effects. The purpose of this study was to extend these previous findings by determining whether, when administered together, these two drugs have mutually antagonistic effects on task performance. Two experiments are reported, both using within-subjects double-blind Latin Square designs. In the first, six subjects received single and combined doses of scopolamine 1.2 mg and nicotine 1.5 mg, and there was some evidence that the two drugs had mutually antagonistic effects on the rapid information processing task. In the second experiment 12 subjects received the same doses, but rapid information processing testing was carried out over a longer time period and Stroop testing was introduced at the end of the 2.5 h session. Nicotine was found to counteract the depression of performance produced by scopolamine on both the rapid information task and the Stroop test. These results provide further support for the theory that central cholinergic pathways play a major role in human information processing.     

Nicotine administration in rabbits using Habitrol nicotine patches and nicotine nasal spray

1. Several methods are used to provide predictable and effective nicotine to experimental animals in scientific studies. Due to the expense and technical challenges of these methods, we sought suitable alternatives. Consequently, the purpose of the present study was to develop a reliable experimental nicotine protocol in rabbits that included either Habitrol nicotine patches (Novartis Consumer Health Inc., Summit, NJ, USA) or nicotine nasal spray. 2. Administration of one of three doses of nicotine (2.5, 5, or 10 mg) was accomplished daily on 13 rabbits divided between either the patch or spray groups. Systemic nicotine and cotinine levels at 0 h, 15 min and 8 and 24 h were assayed. Data were analysed by a Fisher's protected least significant difference test at P = 0.05. 3. Rabbits treated with Habitrol patches exhibited consistent and predictable systemic nicotine levels. The nicotine nasal spray produced an immediate dose-dependent response with no measurable nicotine serum levels at 8 h. 4. For nicotine administration in rabbits, nicotine patches are easy to administer and provide a nicotine serum level between 5 and 25 ng/mL, which is consistent with the average daily level found in a patient who smokes cigarettes.     

The effects of smoking on performance on the Garner speeded classification task

The Stroop task has been used by several investigators to examine the effects of nicotine and smoking on human selective attention, but this research has produced inconclusive results. In this article a new task is described, the Garner speeded classification task, that can be used to explore the influences of nicotine on human selective attention in a more detailed fashion than has been reported previously. In a study using this task reported here, 52 smokers performed the Garner task twice. Half the subjects smoked a cigarette between the first and second completion of the task, and the remainder did not smoke. The main findings were that smoking reduced the size of Garner interference for both reaction time and error measures, and that smoking reduced the size of Stroop interference for the error measure but not the reaction time measure. The degree of nicotine deprivation of the subjects at testing did not substantially affect this result. Moreover, there was a suggestion that the effect of smoking on Stroop interference was secondary to the effect on Garner interference, indicating that smoking, and thus presumably nicotine, principally attenuates the disruptive influence of task-irrelevant, but varying, dimensions in selection. © 1998 John Wiley & Sons, Ltd.     

Recovery cycle of the Hoffmann reflex of tobacco smokers and nonsmokers: relationship to plasma nicotine and cotinine levels

Ten normal adult tobacco smokers and 10 non-smoking volunteers 20–31 years of age were the subjects of this study. The tobacco smokers all had a history of daily tobacco smoking. They were asked to stop smoking for 12 hours prior to testing. The Hoffmann (H) reflex and its recovery cycle were measured on different days before and just after smoking one nonfiltered 0 mg, low (0.27 mg), or high (2.16 mg) nicotine containing cigarette in a randomized order. Blood samples were drawn immediately after the H reflex recordings in the tobacco smokers. The blood samples were centrifuged, the plasma removed, frozen, and later assayed for nicotine and cotinine levels.Nonsmokers compared to tobacco smokers before smoking only had a tendency for enhanced amplitude of the recovery cycle. After smoking the nicotine containing cigarettes, the tobacco smokers had a depression of the amplitude of the H reflex recovery cycle. The amplitude of the H reflex recovery cycle at 160 ms was reduced. This decreased significantly with increasing plasma nicotine and cotinine concentrations. Individual differences were marked.The data obtained are consistent with evidence in animals that nicotine and tobacco smoke stimulate Renshaw inhibitory neurons in the spinal cord, either directly or indirectly which leads to a skeletal muscle relaxant effect.     

Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers

In a double-blind placebo-controlled cross-over study the effects of two doses of subcutaneous nicotine and saline were compared on a range of performance measures in 18 abstaining smokers and 18 never-smokers. Each subject received two injections (40 min apart) of saline, 0.3 mg nicotine, or 0.6 mg nicotine in a balanced order over three sessions. Performance was assessed before and after the injections on nine tests [news recall, Sternberg memory task, finger tapping, logical reasoning, rapid visual information processing (RVIP), long-term word recognition, digit recall, Stroop test, and critical flicker fusion threshold]. In the abstinent smokers, nicotine produced significantly faster correct responses on the logical reasoning test, more target hits, faster reaction times and improved sensitivity on the RVIP task, and more correct responses on word recognition. In never-smokers, nicotine produced faster reaction times on the RVIP and digit-recall tasks, although in the latter case this was at the expense of fewer correct responses. There were no significant differences between the two groups’ responses to nicotine but smokers performed worse than never-smokers prior to injections, even controlling for background characteristics. These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.     

Effects of topiramate in combination with intravenous nicotine in overnight abstinent smokers

Rationale Topiramate, an anticonvulsant medication, may be effective as a treatment for alcohol and cocaine addiction. While a recent clinical study has demonstrated the potential utility of topiramate for smoking cessation in alcohol-dependent smokers, the effects of topiramate on tobacco addiction have not been systematically examined in humans. Objectives To determine topiramate’s effects on acute physiological and subjective responses to intravenous (IV) nicotine in overnight abstinent smokers. Methods Seven male and five female smokers participated in a double-blind, placebo-controlled, crossover study, which consisted of one adaptation and three experimental sessions. Before each session, participants were treated orally with either a single 25 or 50 mg topiramate dose or with placebo. Starting 2 h following the medication treatment, participants received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV nicotine. Results Topiramate treatment at 50 mg, compared to 25 mg or placebo, attenuated heart rate increases induced by nicotine. Topiramate, compared to placebo, enhanced the ratings of subjective effects from nicotine including “drug strength,” “good effects,” “head rush,” and “drug liking.” Topiramate treatment did not affect performance on the Stroop test. Conclusions These results suggest that topiramate may enhance the subjective effects of nicotine and attenuate the heart rate response to nicotine. While the exact mechanisms are unclear, enhancement of the dopaminergic system and attenuation of the noradrenergic system may mediate the topiramate’s effects on the subjective and cardiovascular responses to nicotine, respectively. The utility of topiramate for smoking cessation needs to be examined further in controlled clinical trials.     

Behavioral economics of drug self-administration

The maintenance of a characteristic level of nicotine in a smoker's body is referred to as nicotine regulation. Considerable research has examined this question of whether smokers regulate nicotine intake. This is because nicotine regulation raises the question of whether smokers who, to decrease their intake of tar, switch to low tar/low nicotine cigarettes will increase the number and/or intensity of cigarettes smoked. Although the results of studies examining nicotine regulation are reported as generally consistent, considerable variability exists across these analyses such that the health hazards of smoking low tar/nicotine cigarettes remains uncertain. In the present analysis, these studies were analyzed to ascertain whether a behavioral-economic interpretation could better quantify the effects of changing nicotine yield on individuals' nicotine and smoke consumption. Specifically, 17 nicotine-regulation studies were reanalyzed using a unit-price analysis (i.e., cost-benefit analysis). The reanalysis showed less variability across regulation studies than previously reported; a positively-decelerating demand curve was found across most studies, consistent with previous unitprice analyses of food- and drug-maintained behavior. The benefits of this reanalysis versus the traditional regulation interpretation are that the behavioral economics approach: 1) brings unity to a variable set of data, 2) shows a nonlinear relationship, previously considered to be linear, between nicotine consumption and nicotine yield, 3) shows that nicotine yields higher, and not lower, than the smoker's usual brand decrease smoke consumption and thus decreases consumption of the harmful agents in tobacco, 4) better quantifies the data and provides a more parsimonious interpretation that generalizes to other drugs and food-maintained behavior in humans and nonhumans and, 5) integrates behavioral and pharmacological factors that control the consumption of reinforcers. These results suggest the value of behavioral economics in the study of consumptive behaviors and clinically suggest, in agreement with the studies contained herein, that decreasing the smoker's usual nicotine yield can have potential healthrisks for smokers who are unable to stop smoking.     

Discriminative stimulus effects of intravenous nicotine in squirrel monkeys

Three squirrel monkeys were trained to emit one response after IV administration of nicotine (0.1 or 0.18 mg/kg depending on the subject) and a different response after IV administration of saline. Subjects emitted nicotine-appropriate responses with substitutions of higher doses, but only emitted saline-appropriate responses after substitutions of lower doses. Discrimination performance was then maintained at 0.1 mg/kg of nicotine in all subjects. Neither morphine nor cocaine substituted for the effects of nicotine in any subjects across a range of doses up to those that suppressed responding. Ethyl-beta-carboline-3-carboxylate, an inverse agonist at the benzodiazepine receptor, substituted or partially substituted for nicotine in both subjects in which it was studied.