Biomedical subjects

Kenneth A Perkins

Publications and source records attributed to Kenneth A Perkins.

26 records · Page 2Linked to original sources

PubMed2003

The consistency of acute responses to nicotine in humans.

Nicotine has many acute subjective, physiological, and behavioral effects in humans, some of which may explain why nicotine produces dependence. Individual differences in the magnitude of these effects (i.e., nicotine sensitivity) are of interest to many researchers, such as those examining vulnerability to dependence and processes related to chronic tolerance. However, such characterization of individual differences depends on the consistency of the observed responses, and the consistency of acute effects of nicotine in humans has not been studied systematically. We examined the consistency of the acute effects of the same dose of nicotine administered by nasal spray across multiple drug administration trials, within as well as between sessions. Subjective (i.e., self-reported effects), cardiovascular, and performance measures were assessed following each of four dosing trials of nicotine (20 microg/kg) on three sessions and of placebo on one session. For those measures in which the main effect of nicotine vs. placebo was significant, intraclass correlations were calculated for different sets of trials across different numbers of sessions. Our objective was to determine whether the consistency of responses declined when those responses were based on smaller numbers of trials or sessions, in an effort to guide future research in this area. Results indicated that the consistency of nicotine effects is generally high, even across trials within just one session. Additional research is needed to determine the generalizability of these findings to other methods of nicotine administration, including smoking, and to clarify the extent to which this consistency reflects characteristic consistency of the pharmacological actions of nicotine per se vs. consistency of nonspecific responses to the drug administration procedure.

Administration, Intranasal↗

PubMed2002

Environmental stimuli promote the acquisition of nicotine self-administration in rats.

RATIONALE: Environmental stimuli associated with drugs of abuse are believed to play a major role in the motivation to take drugs, drug dependence, and relapse. Previous work from this laboratory demonstrated that the response-contingent presentation of drug-related, visual cues was at least as important as nicotine in the maintenance, extinction and reacquisition of self-administration in experienced rats. OBJECTIVES: In the present research, we asked whether these same visual cues are effective in promoting the acquisition of operant responding in drug naive rats. METHODS: Male Sprague-Dawley rats were tested for self-administration of IV nicotine (0.03 mg/kg, free base) in 1-h daily sessions when infusions were or were not paired with two lighting events: a 1-s cue light, followed by a 1-min period during which the chamber light was turned off and responding was not reinforced. RESULTS: Rats tested with cues plus nicotine rapidly acquired self-administration and increased their lever pressing rates as the schedule progressed from FR1 to FR5. Without cues, the rate of nicotine self-administration was low and no adjustments were made in response to increasing schedule demands. While one of the stimuli, turning off the chamber light, was shown to have primary reinforcing properties, its association with nicotine produced a synergistic enhancement of lever pressing. Acquisition of operant responding was also enhanced, but to a lesser extent, by a previously neutral compound stimulus, i.e. the nicotine-paired cue light presented with a 1-s tone. CONCLUSIONS: These results illustrate a powerful interaction between environmental stimuli and nicotine in the acquisition of operant responding and indicate that both intrinsically reinforcing and previously neutral cues can participate in this effect.

Animals↗

PubMed2002

Sex differences in the subjective and reinforcing effects of cigarette nicotine dose.

RATIONALE: Some research with novel nicotine delivery methods suggests that nicotine itself may be less reinforcing in women than in men. However, sex differences in the reinforcing effects of nicotine dose via cigarette smoking have received little attention. OBJECTIVES: Sex differences in the subjective and reinforcing effects of smoking were examined as a function of two cigarette nicotine "dose" levels (moderate - subjects' preferred brand, > or = 0.7 mg yield; low - Carlton "ultra-light", 0.1 mg yield). METHODS: Male and female smokers ( n = 30) participated in three sessions, the first two involving independent assessment (only one brand available), and the third involving concurrent assessment (both brands available), of subjective ratings (e.g. "liking") and reinforcement for the two cigarette brands. Subjects were blind to the brand of each cigarette, and subjects abstained overnight prior to each session. Reinforcement was determined by responses on a computer task to earn single puffs on the designated cigarette. RESULTS: Subjective ratings differed between the low versus moderate cigarette nicotine dose under both independent and concurrent assessment conditions, as expected. Notably, this dose difference was smaller in women than in men (i.e. significant sex by dose interactions). The dose effect on smoke reinforcement also was smaller in women than men, but only under the independent and not concurrent assessment condition. CONCLUSIONS: These results indicate that cigarette nicotine dose is a less important influence on the subjective and, under some conditions, reinforcing effects of smoking in women than in men.

Adult↗

PubMed2002

Importance of nonpharmacological factors in nicotine self-administration.

There is mounting evidence that nonpharmacological factors critically modulate the effects of several drugs of abuse both in humans and experimental animals. This paper reviews research from this laboratory on one factor that influences the degree to which nicotine is self-administered: environmental stimuli that form the context within which nicotine is taken. The results suggest that the direct, pharmacological actions of nicotine are necessary but not sufficient to explain either the high rates of self-administration exhibited by laboratory animals or cigarette smoking by humans, and that future investigations on the neurophysiological effects of nicotine that underlie smoking behavior must take into account the environmental context within which the behavior occurs.

Animals↗

PubMed2002

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.

Administration, Intranasal↗

PubMed2002

Chronic tolerance to nicotine in humans and its relationship to tobacco dependence.

Chronic tolerance to any drug of abuse traditionally has been thought critical to understanding drug dependence. This paper reviews research on chronic pharmacodynamic tolerance to nicotine in humans. An overview of tolerance and a discussion of methodological issues are first presented, followed by examination of cross-sectional comparisons of tolerance between groups differing in smoking history, as well as the few prospective studies of change in tolerance after quitting smoking. The relationship of nicotine tolerance to tobacco dependence is then evaluated. While somewhat modest in size, the literature on chronic tolerance to nicotine in humans is reasonably consistent in showing clear evidence of tolerance to subjective mood effects but little or no tolerance to cardiovascular, performance or other nicotine effects, within the limitations inherent in most human research on tolerance. However, this research also indicates that chronic tolerance to nicotine is not closely associated with tobacco dependence: non-dependent and dependent smokers are equally tolerant; tolerance declines very little even years after quitting; and tolerance before quitting may have no relationship to clinical outcome of a cessation attempt. Recent research from the alcohol and substance abuse fields is consistent with the notion that tolerance has little clinical utility in determining dependence. These results question the relevance of nicotine tolerance to dependence and suggest that research into mechanisms of tolerance, while important for understanding biological adaptation, may not elucidate factors responsible for nicotine dependence. Future research should focus on whether dependence may be related to tolerance or to other, as yet unexamined, effects of nicotine, including conditioned tolerance effects, and on the possibility that tolerance may influence the early onset of dependence in teens even if apparently unrelated to maintenance of dependence in adult smokers.

Cross-Sectional Studies↗

PubMed2002

Effects of smoking status and smoking cessation on leptin levels.

Cigarette smoking is associated with lower body weight, and quitting smoking typically produces weight gain. An effect of chronic smoking on increasing leptin, a protein product associated with reducing weight, may help explain this influence of smoking on lowering body weight. We examined fasting serum leptin levels in male and female adult smokers (n = 52) and non-smokers (n = 12) as well as long-time ex-smokers (n = 13), with all groups similar in body mass index (BMI). Partial regression analyses controlling for BMI and, where relevant, age were used to relate leptin to indices of smoking exposure and dependence within the smokers, and with typical alcohol and caffeine intake in the entire sample. Furthermore, a subset of the smokers (n = 22) quit for at least 3 weeks, and changes in leptin and weight were prospectively assessed. Results showed no difference in mean leptin levels as a function of smoking status and no significant associations of leptin with smoking exposure variables after controlling for BMI and age. However, leptin was significantly correlated with alcohol intake (inversely) in women. In addition, smoking cessation increased leptin, the opposite change expected if leptin were responsible for weight gain, but again only in women and not in men. This leptin change remained significant after controlling for the increase in weight observed in both men and women. In conclusion, the influence of cigarette smoking on body weight does not appear to be due directly to changes in leptin levels, as there is no difference in leptin due to smoking status and leptin does not decline after cessation.

Adult↗

PubMed2000

Tobacco withdrawal in women and menstrual cycle phase.

Because negative mood is a characteristic of both tobacco withdrawal and menstrual discomfort, withdrawal may vary by menstrual cycle phase. Tobacco withdrawal, mood, and menstrual discomfort were assessed in premenopausal women who quit smoking during either the follicular (Days 1-14 postmenstrual onset; n = 41) or luteal (Day 15 or longer postmenstrual onset; n = 37) phase of the menstrual cycle and maintained biochemically verified smoking abstinence during the postquit week. Women quitting during the luteal phase reported significantly greater increases in tobacco withdrawal and self-reported depressive symptoms than women quitting during the follicular phase. These results indicate that selecting a quit-smoking day early in the follicular phase may attenuate withdrawal and negative affect in premenopausal female smokers.

Adult↗