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Biomedical subjects

K A Perkins

Publications and source records attributed to K A Perkins.

At least 55 records · Page 3Linked to original sources

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 micrograms/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.

Adult↗

Different methods of assessing nicotine-induced antinociception may engage different neural mechanisms.

Two methods were used to assess nicotine-induced antinociception: tail withdrawal from a hot water bath and hind paw withdrawal from a hotplate. Nicotine doses which produced 75-80% maximum response were 0.75 mg/kg (free base) for tail withdrawal and 0.35 mg/kg for paw withdrawal. The peripheral blocker chlorisondamine (0.1 mg/kg, SC) and the central antagonist, mecamylamine (1 mg/kg, SC) were each effective in blocking nicotine-induced increases in tail withdrawal latencies, suggesting that this effect of nicotine depends on either the action of nicotine at peripheral receptors or the functional integrity of those receptors. In contrast, nicotine-induced increases in paw withdrawal latencies were blocked by mecamylamine but not by chlorisondamine, even at other agonist/antagonist dose combinations. The results indicate that these two effects of nicotine involve at least partially separate pathways and may reflect a different mix of the antinociceptive and motor depressing effects of nicotine.

Analgesia↗

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 smoking's acute influence on reducing food intake does not reflect a broad gender difference but may be specific to dietary restraint.

Adolescent↗

Influence of aerobic fitness, activity level, and smoking history on the acute thermic effect of nicotine.

Individual variability in sensitivity to the acute thermic effects of nicotine has been difficult to study because of methodological limitations in the use of smoking to manipulate nicotine dose. This study examined the influence of smoking history, body composition, and, in a subset of subjects, aerobic fitness and physical activity on the thermic effect of nicotine using a measured-dose nasal spray procedure. Following overnight fasting and smoking abstinence, 38 healthy male smokers were intermittently administered a nicotine dose corrected for body weight (15 micrograms/kg, approx. 1.1 mg for average subject) or placebo on separate occasions in a within-subjects study. Indirect calorimetry was used to assess resting energy expenditure (REE) before and after dosing. Acute thermic response to nicotine ranged from -4.3 to +10.8 kcal/h (-5.4% to +12.6% of REE). Thermic response to nicotine was correlated significantly with aerobic fitness (r = 0.58, p < 0.005), physical activity (r = 0.44, p < 0.05), and number of pack-years of smoking (r = 0.43, p < 0.01). Thermic response was marginally correlated with percent body fat (r = -0.23, p < 0.10), but not with body weight (r = 0.04), percent of ideal weight for height (r = -0.10), or lean body mass (r = 0.05). These results indicate that male smokers higher in fitness and activity and with greater smoking exposure histories may experience greater increases in energy expenditure as a result of nicotine intake via smoking. Consequently, variability in these characteristics could help account for some of the variability in weight gain after stopping smoking.

Adolescent↗

Physiological and subjective responses to food cues as a function of smoking abstinence and dietary restraint.

Dietary restraint is a characteristic associated with greater increase in food intake after smoking cessation, and salivation is a marker of physiological responsiveness to food that may be influenced by cessation. The present study examined the effect of brief smoking abstinence (16 h) vs. no abstinence on salivary and subjective responses to food taste cues in women smokers high vs. low in dietary restraint (n = 10 each). On each of two days (smoking abstinence vs. nonabstinence), salivary volume was assessed during each of 10 trials involving presentation of a small sample of strawberry yogurt. Decline in salivation over trials is indicative of habituation, or reduction in physiological responsiveness to taste cues, and may be a marker of satiety. Subjects also completed self-report measures of hunger, taste liking, desire for cigarette, and emotional arousal during each trial. A 10-min period of ad lib consumption of yogurt ended each session. Results showed significantly elevated salivary response to the first trial of taste exposure in high vs. low restraint women, especially on the smoking day. Moreover, salivary habituation was significantly disrupted by smoking abstinence, especially over the first 5 trials, in high restraint but not low restraint women. High restraint women also reported increasing desire for cigarette and emotional arousal across food taste trials on both days, while low restraint women reported no change in each over trials. There were no differences in ad lib yogurt consumption. These results indicate that brief smoking abstinence attenuates salivary habituation to taste in high restraint women, suggesting a marker for processes responsible for increased food intake after quitting smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Acute effects of tobacco smoking on hunger and eating in male and female smokers.

Cigarette smoking is associated with reduced body weight, an effect which has often been attributed to acute anorectic actions of nicotine. In this study, male and female smokers (n = 10 each), abstinent overnight from smoking and food, participated in three 2-h sessions, involving intermittent, controlled exposure to their usual cigarette (mean yield = 0.75 mg nicotine), a very low nicotine cigarette (0.1 mg) or an unlit cigarette. Hunger and cigarette craving were assessed throughout each session, which ended with ad libitum consumption of a variety of food items ("lunch"). Plasma nicotine analyses confirmed successful control of nicotine exposure via smoking. Results indicated no differences across cigarette conditions in hunger, in contrast to the sharp differences in cigarette craving. There were no differences in total caloric intake, or in macronutrient or taste selection. There were also no differences in any responses to smoking condition as a function of gender. These findings cast into question the commonly held notion that nicotine or smoking has acute anorectic actions in smokers.

Adult↗

Subjective and cardiovascular responses to nicotine combined with caffeine during rest and casual activity.

Although nicotine and caffeine have separately been shown to acutely increase subjective arousal, their combined effects are unclear. Furthermore, their effects during casual physical activity, the condition under which individuals usually experience nicotine and caffeine, are unknown. Smokers who were regular coffee drinkers (n = 19, 9 males, 10 females) participated in eight morning sessions, involving nicotine/placebo, caffeine/no caffeine, and rest/physical activity (i.e. 2 x 2 x 2 within-subjects design). Nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaf coffee with or without added caffeine (5 mg/kg), followed by subjective [Profile of Mood States (POMS), Stress-Arousal Checklist, visual analog scales] and cardiovascular (heart rate, blood pressure) measures. Casual physical activity was standardized by low-intensity bicycle riding while sitting comfortably. Results indicated significant subjective and cardiovascular effects of nicotine and caffeine individually, with the combination of nicotine and caffeine generally producing additive or greater than additive effects for each measure. However, activity mediated some of the subjective effects of nicotine, as nicotine appeared to be "stimulating" during rest but not during activity. There were no differences between males and females. These findings suggest that nicotine per se and caffeine generally have additive subjective and cardiovascular effects, and that nicotine may influence subjective stimulation differentially depending on whether a smoker is resting or engaged in casual activity.

Adult↗

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 micrograms/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 micrograms/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 micrograms/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.

Adult↗

Comparison of acute subjective and heart rate effects of nicotine intake via tobacco smoking versus nasal spray.

Nicotine is the primary psychoactive constituent of tobacco smoke, but it is not clear whether the reinforcing effects of cigarette smoking can be attributed solely to nicotine intake. In this study, two groups of male and female smokers participated in three sessions involving intermittent exposure to moderate low, or no nicotine doses via controlled tobacco smoking ("smoke," n = 20) or measured-dose nasal spray ("spray," n = 16). Visual analog scales of subjective effects (VAS) and heart rate (HR) were obtained within 5 min of each dosing. Plasma nicotine levels indicated comparable dosing between methods. For both methods, there were significant nicotine dose effects for most subjective measures and HR. More importantly, the pattern of effects across doses was virtually identical between methods, as nicotine intake via smoking or spray significantly increased HR and the VAS scales of Head Rush and Dizzy, decreased Hunger and Desire to Smoke, and had no effect on Comfortable, Jittery, or Relaxed. These results suggest that rapid nicotine uptake by novel methods may provide effects very similar to nicotine intake by smoking.

Administration, Intranasal↗

Tobacco abstinence, smoking cues, and the reinforcing value of smoking.

One definition of the reinforcing value of a drug is the degree to which an organism will work to obtain it. Male and female smokers (n = 8 each) engaged in a task involving concurrent schedules of reinforcement for responding to receive cigarette puffs versus money on four occasions, following overnight abstinence versus no abstinence and in the presence of a lit cigarette (smoking "cue") or with no cigarette (2 x 2 design). Reinforcement schedule for puffs ranged from variable ratio 4 (VR4) to VR32, with schedule order during the first five trials (VR4 first, VR32 first) counterbalanced and repeated in reverse sequence during the second five trials. Schedule for money remained at VR4 during all trials. Results indicated significantly greater responding for puffs after overnight abstinence and in the presence of the smoking cue, although effect of the cue was specific to the "leaner" VR schedules (VR16, VR32). Unexpectedly, not only was reinforcement schedule for puffs a significant determinant of responding, but the order of these schedules (i.e., VR4 first vs. VR32 first) produced a significant overall difference in responding for puffs, especially in the presence of the cue. There was no difference in responding between males and females. These findings indicate that the reinforcing value of smoking is increased by overnight abstinence, the presence of a lit cigarette under lean reinforcement conditions, and the order in which reinforcement schedules are presented.

Adult↗

Immunological effects of acute and chronic nicotine administration in rats.

We previously demonstrated that acute nicotine administration decreased the response of rat blood leukocytes (PBL) to concanavalin A (ConA). We now extend those findings to a comparison between the effects of acute and prolonged nicotine exposure (ten daily injections), on PBL and splenocytes (SL). A single injection suppressed the PBL response to ConA and phytohemagglutinin (PHA); tolerance developed by ten injections. In contrast, acute nicotine did not affect SL response to ConA and reduced the PHA response only at the highest concentration. Ten nicotine injections enhanced SL responsiveness to PHA. The only change in PBL subsets was an increase in CD8+ cells following ten injections.

Animals↗

Acute thermogenic effects of nicotine combined with caffeine during light physical activity in male and female smokers.

The thermogenic effects of nicotine and caffeine during physical activity compared with rest were examined in male and female smokers (n = 10 each). During eight sessions, nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaffeinated coffee with or without added caffeine (5 mg/kg), followed by assessment of energy expenditure by indirect calorimetry while subjects engaged in standardized, low-intensity cycle ergometer riding (activity) or remained at quiet rest. Results indicated significant thermogenic effects of nicotine and caffeine individually, with the combination of nicotine and caffeine producing additive effects. Expenditure attributable to nicotine, caffeine, or their combination was significantly enhanced during activity compared with rest, but only for males and not females. Plasma nicotine concentrations were influenced by activity and caffeine, but these pharmacokinetic changes did not appear to explain the differences in expenditure. These findings suggest a sex difference in thermogenic effects of nicotine and caffeine during casual physical activity and potentially explain some of the apparent individual variability in expenditure due to tobacco smoking.

Administration, Intranasal↗

Chronic and acute tolerance to subjective, behavioral and cardiovascular effects of nicotine in humans.

Understanding tolerance to effects of nicotine in humans may elucidate processes involved in the onset and maintenance of tobacco dependence. Subjective, behavioral and cardiovascular responses to nicotine were examined as a function of past history of nicotine exposure (i.e., smokers vs. nonsmokers, chronic tolerance) and of immediately preceding nicotine exposure (acute tolerance). Dose-effect relationships between nicotine (0-2 micrograms/kg via measured-dose nasal spray) and each response were determined in male and female smokers (n = 17) and nonsmokers (n = 18), with different doses presented on different days. Each day, subjects also received a challenge dose of 20 micrograms/kg 30 min after the previous dosing to assess acute tolerance. Plasma nicotine concentrations were 30% lower in nonsmokers compared with smokers and analyses were adjusted to control for this difference. Results showed significant changes in nearly all responses as a function of nicotine dose. Dose-effect curves were shifted to the right or dampened in smokers relative to nonsmokers for most subjective and some behavioral responses, consistent with chronic tolerance, but there was less evidence of chronic tolerance to other behavioral effects or to cardiovascular responses. A pattern of acute tolerance generally similar to that of chronic tolerance was observed across response domains (i.e., clear acute tolerance to subjective measures but less to behavioral or cardiovascular effects). These results support the notions that regular use of nicotine is associated with chronic functional tolerance and that repeated nicotine exposure during a single episode produces acute tolerance. A similar pattern of chronic vs. acute tolerance suggests similarity of mechanisms responsible for both "types" of tolerance. However, variability in tolerance magnitude across subjective, behavioral and cardiovascular response domains indicates that different mechanisms may be responsible for these different effects of nicotine.

Adult↗

Acute stress or corticosterone administration reduces responsiveness to nicotine: implications for a mechanism of conditioned tolerance.

We have shown that conditioned tolerance develops to some of the behavioral and endocrine effects of nicotine in rats. Other investigators have suggested that tolerance to multiple nicotine injections in mice may be due, in part, to elevated plasma corticosterone (CORT) levels, since repeated nicotine injections are associated with elevated CORT, chronically elevated CORT reduces nicotine responsiveness and adrenalectomy disrupts nicotine tolerance. Three experiments tested the feasibility of this hypothesis, as a mechanism for conditioned nicotine tolerance in rats, by determining whether acute administration of CORT or manipulations that increase adrenocortical activity reduce nicotine responsiveness. In experiment 1, male rats were injected IP with CORT (1 mg/kg), vehicle (ETOH + distilled water) or no injection 10 min before nicotine (0.75 mg/kg, SC) and tested for nicotine-induced analgesia every other day for 10 days. A significant reduction in withdrawal latencies was obtained for CORT pretreated rats compared to animals given only nicotine. A similar reduction was produced by the vehicle pretreatment, which itself induced an elevation of endogenous CORT. Experiments 2 and 3 established that similar effects could be produced by doses of CORT as low as 0.125 mg/kg or by exposure to a novel environment which also elevated CORT levels. Results also suggest that a conditioned release of endogenous CORT was triggered by stimuli associated with nicotine delivery. These data are consistent with the hypothesis that a conditioned release of CORT could contribute to the development of tolerance to some of nicotine's effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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)

Adult↗

Introduction to special section: clinical research in smoking cessation.

Although tobacco smoking is becoming less common in the United States, it remains perhaps the most important behavioral problem treated by psychologists. Research interest in smoking has greatly increased among psychologists, but success rates of formal treatment programs for smoking cessation have remained stubbornly low. This article introduces a series of 9 reviews that examine the current status of several diverse areas of research in smoking cessation and provide directions for future efforts in these areas in an effort to promote more innovative investigations.

Humans↗

Weight gain following smoking cessation.

Smoking generally suppresses body weight below "normal," and smoking cessation allows weight to return to normal. This weight gain following cessation appears to be due to a transient increase in eating coupled with the removal of acute metabolic effects of each cigarette, with no change in physical activity. Nevertheless, tobacco smoke (and specifically nicotine) does not appear to be simply either an anorectic or a thermogenic agent. Although there may be no easy explanation for the effects of smoking on energy balance, the most parsimonious explanation may be that smoking lowers body weight "set point" and cessation raises set point. The transient changes in eating are therefore secondary to the changes in body weight set point. This notion is supported by animal research with nicotine as well as with other drugs, and it is also supported less directly by the pattern of changes observed with changes in smoking status among humans. A set-point explanation for weight gain after smoking cessation may also help explain the lack of success of interventions designed to prevent this weight gain.

Animals↗

Diet, alcohol, and physical activity as a function of smoking status in middle-aged women.

Diet, alcohol intake, and leisure-time physical activity were compared cross-sectionally in middle-aged female smokers, ex-smokers, and never smokers and were reassessed approximately 3 years later. At initial contact, there were no group differences in total caloric intake and very few differences in nutrient intake, but alcohol intake of current smokers and ex-smokers was at least 50% greater than that of never smokers, and current smokers reported less physical activity than did ex-smokers and never smokers. Prospective findings were similar: Compared with continuing smokers, ex-smokers did not change their dietary and alcohol intake but significantly increased physical activity. Thus, some adverse behaviors associated with smoking (e.g., alcohol intake) may be due to self-selection to history of smoking, whereas other behaviors (e.g., reduced physical activity) may be more directly related to smoking itself.

Age Factors↗