Effects of Cigarette Smoking on Psychopathology Scores in Patients With Schizophrenia: An Experimental Study

Cigarette smoking and/or nicotine administration have been shown to transiently ameliorate several psychophysiological deficits in patients with schizophrenia such as indicators of deficient sensory gating and attention, but acute effects of smoking on positive and negative symptoms in schizophrenia have not been evaluated in experimental paradigms. The current study assessed whether smoking of cigarettes, after 6–12 h abstinence, transiently alters the expression of negative and/or positive symptoms in patients with schizophrenia who have a history of regular smoking. In a double-blind, placebo controlled study patients with schizophrenia participated in two sessions in which they smoked either cigarettes moderately high in nicotine content or denicotinized cigarettes. They were interviewed pre-and postsmoking to obtain ratings of PANSS and SANS scales, and had blood pressure and pulse serially recorded before and after smoking. Pulse rate and blood pressure were slightly higher after smoking in the high nicotine cigarette session. Negative symptom scores on both scales were significantly lower after cigarette smoking compared to same-day predrug baseline, but there were no differences in active versus denicotinized cigarette drug effects. These results suggest that acute smoking of cigarettes reduces negative symptoms in patients with schizophrenia in this experimental paradigm. Future work needs to identify the mechanism responsible for this behavioral effect.     

Effects of cigarette smoking on psychopathology scores in patients with schizophrenia: An experimental study

Cigarette smoking and/or nicotine administration have been shown to transiently ameliorate several psychophysiological deficits in patients with schizophrenia such as indicators of deficient sensory gating and attention, but acute effects of smoking on positive and negative symptoms in schizophrenia have not been evaluated in experimental paradigms. The current study assessed whether smoking of cigarettes, after 6–12 h abstinence, transiently alters the expression of negative and/or positive symptoms in patients with schizophrenia who have a history of regular smoking. In a double‐blind, placebo controlled study patients with schizophrenia participated in two sessions in which they smoked either cigarettes moderately high in nicotine content or denicotinized cigarettes. They were interviewed pre‐and postsmoking to obtain ratings of PANSS and SANS scales, and had blood pressure and pulse serially recorded before and after smoking. Pulse rate and blood pressure were slightly higher after smoking in the high nicotine cigarette session. Negative symptom scores on both scales were significantly lower after cigarette smoking compared to same‐day predrug baseline, but there were no differences in active versus denicotinized cigarette drug effects. These results suggest that acute smoking of cigarettes reduces negative symptoms in patients with schizophrenia in this experimental paradigm. Future work needs to identify the mechanism responsible for this behavioral effect.     

Effects of nicotine nasal spray on cognitive function in schizophrenia.

Schizophrenics have among the highest rates of cigarette smoking. Some studies indicate that cigarette smoking or nicotine may ameliorate some of the cognitive or theoretically related neurophysiological deficits seen in schizophrenic patients. This study investigated the effects of nicotine nasal spray on measures of attention, verbal memory, and visual-spatial memory in schizophrenic patients who were chronic smokers, using a double-blind placebo-controlled pre-post experimental design. Compared to placebo, active nicotine spray significantly decreased reaction time on the Conner's CPT and improved scores on a measure purported to reflect spatial working memory on a dot task. There were trends for the increased number of hits and decreased number of errors in pre-post comparisons on the CPT task in the active nicotine session. There were no effects of active nicotine nasal spray on verbal memory. Our results suggest that nicotine may modestly enhance attention and spatial working memory in schizophrenic patients who are cigarette smokers and have been abstinent overnight.     

A direct test of the influence of nicotine response expectancies on the subjective and cognitive effects of smoking

Regardless of actual nicotine content, expectations about the nicotine content of a cigarette influence the rewarding subjective effects of smoking, and may even affect cognitive performance. These effects are theorized to be mediated by beliefs about effects of cigarette smoking, or response expectancies. However, few studies have directly manipulated response expectancies. Understanding the effects of such manipulations could improve effectiveness of nicotine-dependence treatments and medications. Using a 2 × 2 between-subjects factorial design, cigarette smokers (N = 80) smoked either a nicotine or a placebo (denicotinized) cigarette crossed with instructions that the cigarette would either enhance or impair cognitive and motor performance. As predicted, participants in the "told enhance" condition reported significantly greater beliefs that nicotine had beneficial effects on performance than those in the "told impair" condition. Compared to those "told impair," those "told enhance" reported more psychological reward, enjoyable physical sensations, and craving reduction from the cigarette, as well as greater motivation to perform well on a cognitive task. Relative to placebo cigarettes, nicotine cigarettes produced greater reports of satisfaction, craving reduction, and dizziness. Smoking a nicotine cigarette produced better performance on the Rapid Visual Information Processing Task, a test of sustained attention; but the expectancy manipulation had no effect. These data suggest that response expectancies can be experimentally manipulated and can influence perceived rewarding effects of cigarette smoking, but do not appear to affect cognitive performance. These findings add to our understanding of the benefits and limitations of expectancy manipulations, both experimentally and as a treatment technique. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Substitutes for tobacco smoking: a behavioral economic analysis of nicotine gum, denicotinized cigarettes, and nicotine-containing cigarettes

Both pharmacological and nonpharmacological stimuli may be responsible for the reinforcement and maintenance of tobacco smoking. The present study examined the self-administration of nicotine gum, denicotinized cigarettes, and nicotine-containing cigarettes utilizing a behavioral economic design in order to investigate the pharmacological and nonpharmacological aspects of cigarette smoking. Cigarette-deprived, dependent smokers worked for cigarette puffs and nicotine gum in daily operant sessions. In one phase, nicotine-containing cigarettes were available at increasing unit prices across sessions. Three phases replicated these sessions with nicotine gum, denicotinized cigarettes, or both, concurrently available at a constant unit price. As nicotine-containing cigarette unit price increased, consumption decreased. However, as nicotine-containing cigarette unit price increased, nicotine gum and denicotinized cigarette consumption increased. Consumption of nicotine gum, but not denicotinized cigarettes, diminished when all three reinforcers were concurrently available. Concurrently available denicotinized cigarettes, but not nicotine gum, caused a statistically significant reduction in nicotine-containing cigarette consumption. In another phase, denicotinized cigarettes were available at increasing unit prices across sessions while nicotine gum was concurrently available at a constant unit price. This phase demonstrated that nicotine content had no reliable effect on cigarette or nicotine gum consumption. These results suggest that denicotinized cigarettes are a more effective alternative reinforcer than nicotine gum, indicating that nonpharmacological stimuli of smoking merit attention in smoking cessation treatment. Furthermore, these findings indicate that alternative reinforcement would be most effective in smoking cessation treatment when combined with high prices for cigarettes.     

The influence of nicotine dose and nicotine dose expectancy on the cognitive and subjective effects of cigarette smoking

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A'). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence.     

Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving,Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.     

Effects of smoking/nicotine on performance and event-related potentials during a short-term memory scanning task

RATIONALE: Nicotine absorbed from cigarette smoke shortens reaction time (RT) in a wide variety of cognitive tasks. However, relatively few studies have tried to isolate the specific stage(s) of information processing affected by smoking/nicotine. OBJECTIVE: The present study was designed to investigate the effect of smoking/nicotine on the short-term memory (STM) scanning stage of information processing in minimally abstaining smokers. Both RT and event-related potentials (ERPs) were measured. METHODS: A Sternberg-type STM-scanning task was performed before and after smoking each of two cigarettes. One cigarette had a 0.05-mg nicotine yield ("denicotinized") and the other had a 1.1-mg yield ("nicotine-yielding"). On each trial, either 2, 3, or 4 consonants were displayed as a memory set. After a brief interval, a single probe consonant was displayed. If the probe was in the memory set (positive probe) a right button press was required, and if the probe was not in the memory set (negative probe) the left button was pressed. RESULTS: Smoking the nicotine-yielding cigarette but not the denicotinized cigarette shortened RT. However, memory-scanning speed, as estimated from the increase in RT as a function of increasing set size, was not differentially affected by the two types of cigarettes. For the ERPs, smoking the nicotine-yielding but not the denicotinized cigarette (a) reduced N200 latency to both the memory-set stimuli and negative probes, (b) increased N200 amplitude to negative probes and P300 amplitude to both types of probes, and (c) produced a sustained negative shift in memory-set ERP amplitude beginning around 600 ms post-stimulus. CONCLUSION: While smoking/nicotine shortened probe RT, it did not affect the speed of STM scanning. Moreover, the ERP-latency effects obtained for the probes were small relative to the effects of smoking/nicotine on RT, suggesting that smoking/nicotine shortens RT primarily by affecting response-related processes.     

Placebo cigarettes in a spaced smoking paradigm

Existing evidence supports the notion that nicotine delivery and recentness of smoking mediate the effects of smoking, including decreases in tobacco craving. However, smoking placebo (denicotinized) cigarettes decreases tobacco craving after overnight abstinence. The present study tested whether the recentness of smoking was an important determinant in the ability of a placebo cigarette to reduce tobacco craving. Placebo (0.07 mg nicotine) and conventional (1.1 mg nicotine) cigarettes were used in a spaced smoking paradigm. In six experimental sessions lasting 240 min, subjects smoked either a placebo or conventional nicotine cigarette in intervals of either 30, 60, or 240 min. Heart rate (HR), exhaled carbon monoxide (CO) levels, and subjective (Schuh-Stitzer, QSU) measures of tobacco craving were obtained throughout the spaced smoking paradigm. HR and CO levels increased after smoking both types of cigarettes. Increasing the interval since the last cigarette significantly (p<0.001) increased the baseline values of tobacco craving. Smoking either the placebo or the conventional cigarette caused a significant (p<0.01) reduction in the craving score after smoking. However, the nicotine yield of the cigarette did not influence these patterns. It is concluded that acute tobacco cravings can be repeatedly diminished with cigarettes that do not deliver nicotine.     

Placebo cigarettes in smoking research

This review outlines the development and use of placebo cigarettes in smoking research. Research on effects of smoking has been disadvantaged by the lack of an adequate placebo condition. Recently, tobacco-based denicotinized cigarettes have been used in smoking research to distinguish effects of smoking due to the delivery of nicotine, other components of tobacco smoke, and the sensory process of smoking. Placebo cigarettes do not increase heart rate and blood pressure or produce electroencephalogram changes ordinarily associated with nicotine. However, placebo cigarettes reduce subjective measures of tobacco craving, desire to smoke, and tobacco withdrawal. These findings indicate that the effects of cigarette smoking are dependent on the delivery of nicotine, tar, other compounds of tobacco smoke, and the sensory stimuli. The next generation of research may begin to investigate the mechanisms that modulate these placebo effects.     

Facial EMG as an index of affective response to nicotine

Negative affect reduction has been postulated to be a key feature of cigarette smoking. In the present study, facial electromyography (EMG), heart rate (HR), and skin conductance response (SCR) were used to evaluate the affective significance of acute nicotine administration and overnight withdrawal. Smokers (N = 115) attended four 90-min laboratory assessment sessions scheduled approximately 3 days apart. The sessions provided a complete crossing of 2 prelaboratory deprivation conditions (12-hr deprived vs. nondeprived) with 2 drug conditions (nicotine vs. placebo nasal spray). During each session, smokers viewed affective slides while facial EMG, HR, and SCR were recorded. Results indicated that for women, nicotine nasal spray resulted in lower corrugator EMG activity during both smoking-deprived and nondeprived sessions, compared with placebo. However, nondeprived women also showed an increase in zygomaticus EMG when given nicotine compared with placebo spray, whereas smoking-deprived women demonstrated a decrease in the zygomaticus response to nicotine compared with placebo. With men, nicotine also appeared to lower corrugator during deprivation, but not nondeprivation, compared with placebo spray, though the contrast only approached significance. With zygomaticus EMG, nicotine spray decreased men's zygomaticus responding during nondeprivation but not during deprivation, compared with placebo spray. The HR results reflected the stimulatory properties of the drug rather than nicotine's affective properties, whereas SCR was unresponsive to our experimental manipulations. The corrugator EMG results support negative reinforcement models of smoking that postulate that acute nicotine use reduces withdrawal-driven negative affect.     

The nicotinergic receptor as a target for cognitive enhancement in schizophrenia: Barking up the wrong tree?

Rationale

Cognitive symptoms have increasingly been recognized as an important target in the development of future treatment strategies in schizophrenia. The nicotinergic neurotransmission system has been suggested as a potentially interesting treatment target for these cognitive deficits. However, previous research yielded conflicting results, which may be explained by several methodological limitations, such as the failure to include both a group of smoking and non-smoking schizophrenic patients, the use of only a single nicotine dose, and the inclusion of a very limited cognitive battery.

Objectives

The present study aims at investigating the cognitive effects of nicotine in schizophrenia while addressing these methodological issues.

Methods

In a double-blind placebo-controlled randomized crossover design, cognitive effects are assessed in smoking (n?=?16) and non-smoking (n?=?16) schizophrenic patients after receiving active (1 or 2 mg) or placebo oromucosal nicotine spray.

Results

A modest improving effect of nicotine on attention in the smoking but not the non-smoking group was found. No enhancing effects were found on measures of visual memory, working memory, processing speed, psychomotor speed, or social cognitive functioning in either patient group.

Conclusions

These findings suggest that the nicotinic receptor only has limited value as a cognitive treatment target in schizophrenia.     

Nicotine withdrawal and psychiatric symptoms in cigarette smokers with schizophrenia.

The prevalence of smoking is markedly elevated in schizophrenia. Low smoking cessation rates and reports that some smokers with schizophrenia experience an acute increase in symptoms during attempts to quit smoking, suggest a self-medication model. Alternatively, smoking may modulate medication side effects. The effects of treated and untreated smoking abstinence on psychotic symptoms and medication side effects were examined in this study. Nineteen outpatients with schizophrenia or schizoaffective disorder participated in a randomized, double-blind, balanced crossover study: 1 day of ad libitum smoking followed by 3 days of acute smoking abstinence while wearing 22 mg/day active or placebo transdermal nicotine patches, with a return to 3 days of smoking between patch conditions. Daily symptom and side-effect ratings, nicotine and cotinine blood levels were collected. Twelve subjects completed the study. Neither positive symptoms nor mood symptoms changed. An increase in negative symptoms during the first abstinent day occurred in both placebo and active patch conditions, but was not sustained over subsequent abstinent days. Despite physiological signs of withdrawal, completers did not endorse increased nicotine withdrawal symptoms. Dropouts reported higher withdrawal symptoms, but also had no increase in psychiatric symptoms in either phase of the study. Of note, dyskinesias decreased during abstinence and placebo patch treatment, but increased during abstinence and the active patch conditions. Acute exacerbation of psychiatric symptoms is an unlikely explanation for any difficulty smokers with schizophrenia have in early abstinence.     

Silver acetate interactions with nicotine and non-nicotine smoke components

Oral topical silver-containing formulations were marketed in the 1970s and 1980s as smoking deterrents, based on the finding that when using such formulations, an unpleasant taste occurs upon smoking. This approach has not been widely adopted, however, in part because of a lack of efficacy data. The advent of new pharmacologic treatments for smoking cessation renews the possibility that such a taste aversion approach may be a useful adjunct to smoking cessation treatment. This study explored the basic mechanistic question of whether topical oral silver acetate solution interacts with nicotine as opposed to non-nicotine smoke constituents. We recruited 20 smoking volunteers to rate nicotine-containing or denicotinized cigarettes, as well as the Nicotrol nicotine vapor inhaler and sham (air) puffs. In two sessions, subjects rated the sensory and hedonic qualities of puffs after rinsing their mouths with either silver acetate solution or deionized water (placebo). Silver acetate relative to placebo solution substantially reduced liking and satisfaction ratings for the usual brand and denicotinized cigarettes; in contrast, for the nicotine inhaler these ratings were unaffected by the silver-based treatment. These results support the conclusion that silver acetate not only renders the taste of cigarette smoke less appealing, but also that the compound appears to interact selectively with non-nicotine smoke constituents. Moreover, these data suggest silver acetate would be compatible with buccal nicotine delivery systems (e.g., nicotine lozenge or gum). Combined use of taste aversion with nicotine replacement therapy could provide the smoker with additional assistance to resist relapse. Further exploration is warranted of the use of silver-based preparations as a short-term adjunct to smoking cessation treatment.     

Lack of reinforcement enhancing effects of nicotine in non-dependent smokers

Rationale  Recent animal research has shown that, aside from its primary and secondary reinforcing effects, nicotine may enhance reinforcement from stimuli unrelated to nicotine intake. Little human research has directly examined this potentially important influence of nicotine. Objectives  We report two virtually identical studies examining the influence of nicotine, via nasal spray (study 1) and cigarettes (study 2), on the reinforcing effects of rewards unrelated to nicotine intake. Materials and methods  Both studies involved young adults with some past smoking exposure but no history of nicotine dependence. Reinforcement was assessed by responses on a simple operant computer task reinforced by: money, music, the termination of aversive noise, or no reward (control). Participants responded for rewards on three separate sessions, involving intermittent dosing of 0, 5, or 10 μg/kg nicotine via nasal spray (study 1) or the smoking of 0.05 or 0.6 mg nicotine cigarettes or no smoking (study 2). Results  Results showed no effects of nicotine, by nasal spray or cigarette smoking, on reinforced responses, although nicotine increased some subjective responses (e.g. head rush/buzzed, liking). Nicotine via smoking also did not influence affect or hedonic ratings of slides varying in mood valence in an exploratory trial in study 2. Conclusions  These results do not support the notion that nicotine per se enhances the reinforcing value of other reinforcers in humans. Any reinforcement enhancing effects of nicotine in humans may be specific to dependent smokers or may be relatively narrow and dependent upon procedural conditions different from those in the current studies.     

Dopamine and opioid gene variants are associated with increased smoking reward and reinforcement owing to negative mood

Negative mood increases smoking reinforcement and risk of relapse. We explored associations of gene variants in the dopamine, opioid, and serotonin pathways with smoking reward ('liking') and reinforcement (latency to first puff and total puffs) as a function of negative mood and expected versus actual nicotine content of the cigarette. Smokers of European ancestry (n=72) were randomized to one of four groups in a 2x2 balanced placebo design, corresponding with manipulation of actual (0.6 vs. 0.05 mg) and expected (told nicotine and told denicotinized) nicotine 'dose' in cigarettes during each of two sessions (negative vs. positive mood induction). Following mood induction and expectancy instructions, they sampled and rated the assigned cigarette, and then smoked additional cigarettes ad lib during continued mood induction. The increase in smoking amount owing to negative mood was associated with: dopamine D2 receptor (DRD2) C957T (CC>TT or CT), SLC6A3 (presence of 9 repeat>absence of 9), and among those given a nicotine cigarette, DRD4 (presence of 7 repeat>absence of 7) and DRD2/ANKK1 TaqIA (TT or CT>CC). SLC6A3, and DRD2/ANKK1 TaqIA were also associated with smoking reward and smoking latency. OPRM1 (AA>AG or GG) was associated with smoking reward, but SLC6A4 variable number tandem repeat was unrelated to any of these measures. These results warrant replication but provide the first evidence for genetic associations with the acute increase in smoking reward and reinforcement owing to negative mood.     

Reinforcement enhancing effects of nicotine via smoking

Rationale

In animals, nicotine enhances reinforcement from stimuli unrelated to nicotine intake. Human research is suggestive but has not clearly shown a similar influence of nicotine.

Objectives

We assessed acute effects of nicotine via smoking on enhancement of positive (money, music) or negative (termination of noise) reinforcers, or no “reward” (control). These different rewards determined the generalizability of nicotine effects.

Materials and methods

Dependent (n?=?25) and nondependent (n?=?27) smokers participated in three sessions, each after overnight abstinence. Using a within-subjects design, sessions involved no smoking or smoking denicotinized (0.05 mg) or nicotine (0.6 mg) Quest^R brand cigarettes. For comparison, a fourth session involved no abstinence prior to smoking one's own brand to gauge responses under typical nicotine satiation. Reinforcement was assessed by responses on a simple operant computer task for the rewards, each available singly on a progressive ratio schedule during separate trials.

Results

The reinforcing effect of music, but not other rewards, was greater due to the nicotine cigarette, compared to the denicotinized cigarette or no smoking. Reinforcement enhancing effects of nicotine did not differ between dependent and nondependent groups, indicating no influence of withdrawal relief. Responding due to acute nicotine after abstinence was very similar to responding to one's own brand after no abstinence.

Conclusions

Acute nicotine intake per se from smoking after abstinence enhances the reinforcing value of rewards unassociated with smoking, perhaps in a manner comparable to ad lib smoking after no abstinence. Nicotine's reinforcement enhancing effects may be specific to certain rewards, perhaps those sensory in nature.     

The influence of instructions and nicotine dose on the subjective and reinforcing effects of smoking

Subjective and reinforcing effects of smoking a cigarette were examined within a 2 x 2 modified balanced-placebo design, which manipulated instructions about nicotine content (i.e., told regular nicotine vs. told low nicotine) and actual nicotine dose (given a regular nicotine brand vs. a denicotinized brand). Most ratings of the nicotine content and reward value of cigarettes were higher for those told regular nicotine versus told low nicotine, and for those given regular nicotine versus given low nicotine. Nicotine and instructions did not affect craving, withdrawal, or smoke-reinforced responding, but instructions affected the number of puffs earned for those given low nicotine (i.e., placebo effect). Thus, verbal information (instructions) can influence some responses to smoking consistent with the presence of placebo and antiplacebo effects.     

Nicotine effect on prepulse inhibition and prepulse facilitation in schizophrenia patients.

Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p=0.008) with no drug by diagnosis interaction (p=0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r=0.59, p=0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p=0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.     

Dissociating nicotine and nonnicotine components of cigarette smoking

To dissociate the sensorimotor aspects of cigarette smoking from the pharmacologic effects of nicotine, smokers rated the subjective effects of nicotine-containing or denicotinized cigarettes, and intravenous (IV) nicotine or saline infusions. Three groups of participants (n=20 per group) received either: (1) continuous nicotine, (2) pulsed nicotine, or (3) saline. Each group was exposed to an IV condition once while smoking a denicotinized cigarette and once while not smoking, in a 3x2 mixed design. A fourth group (n=20) received saline while smoking their usual brand of cigarette. The dose and rate of nicotine administration were individualized based on previous measures of ad lib smoke intake. Denicotinized cigarette smoke significantly reduced craving and was rated significantly more satisfying and rewarding than the no-smoking conditions. IV nicotine reduced craving for cigarettes, and increased ratings of lightheadedness and dizziness. However, no significant satisfaction or reward was reported after IV nicotine. The combination of IV nicotine and denicotinized cigarette smoke produced effects similar to those of smoking the usual brand of cigarette. The results suggest that sensorimotor factors are critical in mediating the immediate subjective response to smoking, and that the immediate subjective effects of nicotine administered in doses obtained from cigarette smoking are subtle. Thus, addressing smokers' needs for both for the sensorimotor aspects of smoking as well as for the direct CNS effects of nicotine may be critical in enhancing smoking cessation treatment outcome.