James E. Grobe

Nicotine discrimination in male and female smokers

Discriminative stimulus effects of nicotine were evaluated in humans using formal behavioral drug discrimination procedures. Male and female smokers (n=9 each) were trained on day 1 to reliably discriminate 0 versus 12 µg/kg nicotine administered by measured-dose nasal spray. All subjects were able to reach criterion performance (at least 80% correct). Generalization of responding across nicotine doses of 0, 2, 4, 8, and 12 µg/kg (approximately 0–0.8 mg for typical subject) was then examined on day 2. Nicotine-appropriate responding was linearly related to dose, and subjects were able to distinguish the smallest dose (2 µg/kg) from placebo. Although there were no differences between males and females in behavioral discrimination, subjective effects were correlated with nicotine discrimination in females but not in males. These findings indicate that humans are able to discriminate among low doses of nicotine per se, that males and females may differ in the stimuli used to discriminate nicotine, and that drug discrimination procedures may be more sensitive than traditional subjective effects measures in distinguishing among low doses of nicotine.

Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers

Nicotine and alcohol are often consumed concurrently by smokers. Each drug alone produces significant subjective and cardiovascular responses, but the effects of the two drugs in combination have rarely been examined. Smokers who were moderate alcohol drinkers (n = 18, 9 males and 9 females) participated in four sessions, involving acute administration of nicotine/placebo and alcohol/no alcohol. Subjects abstained overnight from tobacco and alcohol prior to each session. Nicotine (20 µg/kg per presentation) or placebo was administered by measured-dose nasal spray every 30 min for 2 h following consumption of diet tonic water with or without alcohol (0.5 g/kg). Subjective (visual analog scales, Profile of Mood States, Addiction Research Center Inventory) and cardiovascular (heart rate, systolic and diastolic blood pressure) responses were assessed after each nicotine/placebo administration. Nicotine increased head rush, dizzy, and most stimulant effects (i.e. jittery, tension, and arousal and decreased fatigue and relaxed), while alcohol increased intoxication, head rush, dizzy, and jittery, with no other stimulant effects. Nicotine and alcohol generally produced additive subjective and cardiovascular effects when consumed together, although nicotine attenuated sedating and intoxicating effects of alcohol alone. Furthermore, there were several interaction effects on subjective measures involving gender. Nicotine plus alcohol tended to attenuate some subjective effects due to one drug or the other alone in men but enhanced the effects of either alone in women. These findings indicate that nicotine and alcohol generally have additive subjective and cardiovascular effects, but that men and women differentially respond on some subjective measures to the combination of alcohol and nicotine.

Greater Sensitivity to Subjective Effects of Nicotine in Nonsmokers High in Sensation Seeking

The personality characteristic of sensation seeking is associated with risk of smoking, perhaps because of greater initial sensitivity to nicotine. Young healthy nonsmokers (N = 37) were administered 0, 10, and 20 microg/kg nicotine by nasal spray in 3 separate sessions, and subjective responses were assessed. Sensation-Seeking Scale (SSS) scores were then correlated with these responses. A comparison group of smokers (N = 55) was included to determine whether sensation seeking was associated specifically with initial sensitivity to nicotine or with general sensitivity regardless of past nicotine exposure. SSS subscales, particularly Experience Seeking and Disinhibition, were correlated with subjective responses to nicotine in nonsmokers but generally not in smokers. These findings indicate that sensation seeking is associated with greater initial sensitivity to nicotines subjective effects and may provide directions for further study of individual-differences characteristics that predispose people to the risk of becoming smokers.

Nasal spray nicotine replacement suppresses cigarette smoking desire and behavior

The effects of short‐term nasal spray nicotine replacement in suppressing desire to smoke and ad libitum cigarette smoking behavior were evaluated in male and female smokers. In study I, 10 male and 10 female smokers received intermittent doses of 0, 7.5, 15, and 30 µg/kg nicotine by way of measured‐dose nasal spray, with each dose on a separate day. Self‐reported desire to smoke was significantly suppressed by each nicotine dose compared with placebo, but there were no significant differences among nicotine doses or between men and women. In study II, eight male and eight female smokers received 0, 15, and 30 µg/kg nicotine intermittently and were allowed to smoke their preferred brands of cigarettes ad libitum. Similar to study I, nicotine replacement significantly suppressed number of cigarettes smoked, number of puffs, and carbon monoxide boost and increased latency to smoking, but there were almost no significant differences between the two nicotine doses. Magnitude of smoking suppression attributable to 15 µg/kg tended to be greater in men than in women. However, plasma nicotine concentrations were significantly higher after 15 and 30 µg/kg versus placebo, suggesting only partial compensation in smoking behavior with short‐term nasal nicotine replacement. These findings support the idea that short‐term nicotine replacement decreases smoking desire and behavior, but the findings indicate that smoking behavior is partly influenced by factors other than nicotine regulation.

Nicotine preference in smokers as a function of smoking abstinence.

Overnight smoking abstinence increases desire to smoke and intensity of smoking behavior in smokers, but it is not completely clear that this reflects an increase in reinforcement from the psychoactive effects of nicotine per se. We examined choice of nicotine vs. placebo via nasal spray (Study 1) and nicotine vs. nonnicotine cigarette puffs (Study 2) in separate groups of smokers during each of two sessions, following overnight abstinence vs. no abstinence. In each study, subjects followed a forced choice procedure in which they were instructed to self-administer six sprays/puffs from between the two nasal sprays/cigarettes every 15 min for 2 h following initial exposure to each. In Study 1, choice of nicotine spray (1.5 micrograms/kg per spray) increased significantly following abstinence vs. no abstinence (47 +/- 6% vs. 34 +/- 5%, respectively, p < 0.05). This shift in choice was more pronounced in the subset of smokers (choosers, n = 9 out of 24) who selected nicotine on more than 50% of choices on the abstinent day. Choosers exhibited greater responses to initial nicotine exposure on positive (e.g., pleasant, vigor) but not aversive (e.g., jittery, uneasy) subjective measures, suggesting that greater positive reinforcement from nicotine per se predicted subsequent choice. In Study 2, abstinence similarly increased choice of nicotine vs. nonnicotine cigarette puffs (82 +/- 6% vs. 64 +/- 8%, p < 0.05), although nearly all subjects (12 of 13) preferred the nicotine cigarette following abstinence. These results indicate that choice of nicotine per se, isolated from tobacco smoke, increases significantly after overnight tobacco abstinence.

Acute nicotine reinforcement, but not chronic tolerance, predicts withdrawal and relapse after quitting smoking.

Little research has examined the association of tobacco dependence with nicotine tolerance or reinforcement in a clinical sample. Smokers preparing to quit smoking participated in laboratory sessions to assess nicotine tolerance on subjective, cardiovascular, and performance measures and to assess nicotine reinforcement using a choice procedure. Participants were then provided with individual counseling (but no medication), made a quit attempt, and were followed for 1 year to determine clinical outcome, as determined by postquit withdrawal and days to relapse. Nicotine tolerance was unrelated to either withdrawal or relapse. However, acute nicotine reinforcement was significantly related to both greater withdrawal and faster relapse. Results challenge the common assumption that nicotine tolerance is closely related to dependence but suggest that nicotine reinforcement may have theoretical and clinical significance for dependence.

Chronic and acute tolerance to subjective effects of nicotine.

Tolerance to subjective effects of nicotine may induce novice smokers to increase the magnitude and frequency of their nicotine self-dosing. In this study, smokers (n = 8) and nonsmokers (n = 7) participated in three sessions involving presentation of 0, 7.5, or 15 micrograms/kg nicotine 30 min for 2 h via measured-dose nasal spray, with different doses presented on separate days. Subjective responses were assessed using visual analog scales (VASs) of jittery, light-headed, relaxed, dizzy, and head rush, and the Profile of Mood States (POMS) scales of vigor, confusion, fatigue, tension, and the composite scale of arousal. Smaller responses in smokers vs. nonsmokers were viewed as evidence for chronic tolerance. In addition, on each day subjects received a fifth, challenge dose of 30 micrograms/kg 30 min after the previous dosing. Smaller responses to the challenge dose as a function of increasing prior nicotine dosing during Trials 1-4 were viewed as evidence for acute tolerance. Results showed significant changes in most measures as a function of nicotine dose, and the dose-response curves for most VAS and POMS scales tended to be shifted to the right, or dampened, in smokers relative to nonsmokers, consistent with chronic tolerance. However, smokers and nonsmokers tended to respond to nicotine in opposite directions for POMS scales of vigor and arousal, perhaps reflecting withdrawal relief in smokers. Acute tolerance on a few selected VAS and POMS scales was apparent for both smokers and nonsmokers.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender, dietary restraint, and smoking's influence on hunger and the reinforcing value of food

Smoking may enhance satiety following meal consumption, thereby reducing subsequent eating (i.e., between-meal snacks), especially in women high in dietary restraint. Female smokers (n = 20, 10 high and 10 low restraint) and male smokers (n = 10) participated in two sessions, involving overnight abstinence from food and smoking (smoking abstinence day) or from food only (smoking day), in a within-subjects design. The reinforcing value of food was determined by the number of responses made to obtain food reinforcers (100-kcal snack portions) vs. money using a concurrent schedules computer task. Subjects were given a small caloric load on each day followed by access to food vs. money. On the smoking day, subjects were allowed to smoke every 30 min during the session as well as ad lib before the session. Self-reported hunger was also assessed upon arrival (after fasting) and following the caloric load during each session. Results indicated no effect of smoking on initial hunger rating, after fasting, but hunger ratings following the caloric load declined significantly more during smoking vs. abstinence days for all subjects, consistent with an enhancement of postmeal satiety due to smoking. There was no overall main effect of smoking on food-reinforced responding. However, responding for food was significantly less during the smoking vs. abstinence days for high-restraint females only and not for low-restraint females or for males. These findings indicate that smokings acute influence on reducing food intake does not reflect a broad gender difference but may be specific to dietary restraint.

Sex differences in the acute effects of cigarette smoking on the reinforcing value of alcohol.

Alcohol consumption acutely increases smoking behavior, but the reverse relationship, the acute effects of smoking on alcohol intake, largely has been ignored. We examined whether smoking acutely increases the reinforcing value of alcohol, first in the absence of recent alcohol intake and then following an alcohol pre‐load. Healthy, social‐drinking smokers (n  = 11 men, 14 women) engaged in a computerized task involving concurrent schedules of reinforcement for beer (FR10, 3 oz (90 ml) per reinforcement) or money (FR5 to FR30,

Acute tolerance to nicotine in smokers: Lack of dissipation within 2 hours.

0.20 per reinforcement) during two sessions, one following day‐long ad lib smoking and the other following overnight smoking abstinence. During each session, subjects performed the task in two sets of trials, one before and one after consumption of an alcohol pre‐load, with 60 min between sets. To standardize the alcohol pre‐load, all subjects were led to believe that they had earned 9 oz (270 ml) of beer after the first trial set, which they then consumed before the second set of trials. Compared to responding during the abstinent session, responding for alcohol during the smoking session was no different before the alcohol pre‐load (trial set one) but was significantly greater following the alcohol pre‐load (trial set two), although only in men and not women. Subjective sedation after the alcohol pre‐load was attenuated during the smoking session in both men and women, but attenuated sedation due to smoking was related to subsequent alcohol‐reinforced responding only in men. Additional research is needed to determine the extent to which these effects in men are pharmacological in nature or are conditioned responses to smoking or to consuming a preferred alcoholic beverage.