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Biomedical subjects

Kenneth A Perkins

Publications and source records attributed to Kenneth A Perkins.

At least 19 recordsLinked to original sources
PubMed2006

Guidelines on nicotine dose selection for in vivo research.

RATIONALE: This review provides insight for the judicious selection of nicotine dose ranges and routes of administration for in vivo studies. The literature is replete with reports in which a dosaging regimen chosen for a specific nicotine-mediated response was suboptimal for the species used. In many cases, such discrepancies could be attributed to the complex variables comprising species-specific in vivo responses to acute or chronic nicotine exposure. OBJECTIVES: This review capitalizes on the authors' collective decades of in vivo nicotine experimentation to clarify the issues and to identify the variables to be considered in choosing a dosaging regimen. Nicotine dose ranges tolerated by humans and their animal models provide guidelines for experiments intended to extrapolate to human tobacco exposure through cigarette smoking or nicotine replacement therapies. Just as important are the nicotine dosaging regimens used to provide a mechanistic framework for acquisition of drug-taking behavior, dependence, tolerance, or withdrawal in animal models. RESULTS: Seven species are addressed: humans, nonhuman primates, rats, mice, Drosophila, Caenorhabditis elegans, and zebrafish. After an overview on nicotine metabolism, each section focuses on an individual species, addressing issues related to genetic background, age, acute vs chronic exposure, route of administration, and behavioral responses. CONCLUSIONS: The selected examples of successful dosaging ranges are provided, while emphasizing the necessity of empirically determined dose-response relationships based on the precise parameters and conditions inherent to a specific hypothesis. This review provides a new, experimentally based compilation of species-specific dose selection for studies on the in vivo effects of nicotine.

Animals↗
PubMed2005

Medication screening for smoking cessation: a proposal for new methodologies.

RATIONALE: The purpose of medication screening studies is to quickly and cheaply evaluate the clinical potential of medications, so that promising drugs proceed to large-scale clinical trials and unpromising drugs do not. Screening procedures for smoking cessation medications either are not sufficiently practical or lack clinical validity. Clinical trials have clinical validity but are often impractical as initial tests of efficacy (i.e., screening) or suffer from limited statistical power. The alternative approach of short-term, laboratory-based studies of purported mechanisms of efficacy may overcome some of the practical problems of clinical trials but appear to have limited clinical validity. OBJECTIVES: This commentary identifies some of the limitations of current short-term screening procedures and provides suggestions for improving such studies. RESULTS: Short-term screening studies typically use smokers unmotivated to abstain (i.e., nontreatment seekers) as participants and examine brief medication effects on clinical markers or potential mechanisms of action, including relief of withdrawal and craving during enforced abstinence or on reduction in the reinforcing effects of smoked tobacco. The limitation of these approaches is shown by their insensitivity to effects of nicotine replacement and bupropion, which are effective in clinical trials for smoking cessation. CONCLUSIONS: The clinical validity of short-term screening studies may improve if these studies simulate some clinical trial procedures within practical limitations. Thus, they should recruit smokers motivated to abstain, emphasize smoking abstinence as a primary index of medication response, examine effects over sufficiently long time periods to encompass the drug's mechanism of action, and assess responses in the natural environment. Whether these changes improve the sensitivity of screening studies is testable. Other research aimed specifically at identifying the mechanisms of therapeutic action of a medication may also profit from using this approach of simulating a short-term clinical trial.

Administration, Cutaneous↗
PubMed2005

Sex differences in the influence of nicotine dose instructions on the reinforcing and self-reported rewarding effects of smoking.

RATIONALE: Compared to men, the smoking behavior of women may be less responsive to nicotine and more responsive to nonpharmacological factors, perhaps including verbal information (e.g., dose instructions). OBJECTIVE: This study compared the influence of the presence vs absence of dose instructions on the subjective and reinforcing effects of nicotine via cigarette smoking in men and women. METHODS: Subjects (n=120) abstained overnight from smoking and were randomly assigned to one of four groups. Half of the subjects received nicotine cigarettes (Quest 1, yield of 0.6 mg), and the other half received denicotinized cigarettes ("denic"; Quest 3, yield of 0.05 mg). Furthermore, half of each subsample was accurately instructed they were receiving a "normal nicotine" or a "no nicotine" cigarette, while the other half received no instructions. Subjects completed baseline measures of craving and mood (positive and negative affect), took two puffs from the cigarette after receiving dose instructions or no instructions, and then rated the cigarette's "reward" value (liking, satisfying) and other characteristics. They also repeated the craving and mood measures. Subjects then smoked more of that same brand ad libitum over the next 30 min to measure reinforcement (puff number and latency to first puff). RESULTS: Overall, nicotine increased reward, other cigarette ratings, and positive affect, but did not affect craving or smoking behavior. However, results varied by sex. Dose instructions enhanced the effects of nicotine on smoking reward and reinforcement in women, while instructions tended to dampen or even reverse these effects of nicotine in men (i.e., interaction of sex x nicotine x instructions). CONCLUSIONS: In women but not in men, the influence of nicotine on smoking reward and reinforcement is enhanced by accurate verbal information about the cigarette's nicotine dose. These results are consistent with the notion that the smoking behavior of women, relative to men, may be more responsive to nonpharmacological factors.

Adult↗
PubMed2005

Reduced nicotine reward in obesity: cross-comparison in human and mouse.

RATIONALE: Tobacco use and obesity lead to significant morbidity and mortality. OBJECTIVE: This study was conducted to investigate the factors maintaining smoking behavior in lean and obese individuals by utilizing a mouse/human cross-validation model of nicotine reward. METHODS: In humans, a cigarette choice paradigm was used to examine the relative reinforcing value of nicotine in obese and non-obese smokers. Conditioned place preference (CPP) for nicotine was assessed in mice fed standard low fat rodent chow and mice rendered obese by a high fat diet. RESULTS: In humans, obese smokers self-administered nicotine via cigarettes significantly less often than non-obese smokers and showed attenuated hedonic effects of nicotine-containing cigarettes compared to denicotinized cigarettes. Similarly, mice exposed to a high fat diet did not exhibit nicotine CPP, relative to control mice. mRNA levels for mu-opiate and leptin receptors were also downregulated in the ventral tegmental area of these mice. CONCLUSIONS: Together, these studies provide the first evidence for reduced nicotine reward in obese subjects and suggest that this may be mediated by dietary influences on the endogenous opioid system.

Animals↗
PubMed2005

Sex differences in the contribution of nicotine and nonpharmacological stimuli to nicotine self-administration in rats.

RATIONALE: Sex differences have been reported for the impact of nicotine and nonpharmacological cues on smoking. While nonpharmacological environmental stimuli have also been shown to influence nicotine self-administration in rats, there have been no attempts to examine the impact of sex differences in the contributions of nicotine and nondrug stimuli to this behavior. OBJECTIVES: This experiment investigated sex differences in operant responding for nicotine in rats when drug infusions were delivered either in the absence of, or in combination with, a nonpharmacological stimulus. METHODS: Initially, male and female rats acquired self-administration for nicotine alone across a range of doses (0.03, 0.06, and 0.15 mg kg(-1) inf(-1), freebase). After stable acquisition, nicotine infusions were combined with a weakly reinforcing, compound visual stimulus. RESULTS: While there was no overall effect of dose on active lever responding for nicotine in the absence of the visual stimulus, female rats responded more on the reinforced lever than males at 0.06 and 0.15 mg kg(-1) inf(-1) on an FR5 schedule. However, they also showed increased responding on the nonreinforced lever compared to males at the same doses. Combining nicotine infusions with the visual stimulus doubled responding compared to nicotine alone at 0.03 and 0.06, but not at 0.15 mg kg(-1) inf(-1): this effect was significantly greater for female rats. CONCLUSIONS: These data highlight the prominent contribution of nonpharmacological stimuli to nicotine-reinforced behavior across a range of doses in both male and female rats. They also reveal sex differences in operant responding for nicotine under conditions where a nonpharmacological stimulus is either absent, or combined with drug delivery.

Animals↗
PubMed2005

Effects of different nicotine replacement therapies on postcessation psychological responses.

Transdermal nicotine patch (TN) and nicotine nasal spray (NS) are both efficacious forms of smoking cessation treatment, but have different pharmacokinetic properties and modes of action. To understand better psychological responses to treatment, we investigated the effects of TN versus NS on positive affect, negative affect, and withdrawal symptoms during treatment. Participants were randomly assigned to receive TN (n=172) or NS (n=163) plus seven sessions of behavioral counseling, and completed self-report questionnaires at pretreatment and during treatment. TN participants, but not NS participants, reported significant increases in positive affect during treatment. Increases in negative affect and withdrawal were observed, independent of treatment. Only changes in negative affect predicted relapse by the end of the treatment phase. These findings indicate that, although TN may enhance positive affect for smokers in treatment compared with NS, only changes in negative affect predict treatment outcome.

Administration, Cutaneous↗
PubMed2005

Subjective and reinforcing effects of smoking during negative mood induction.

Two notions strongly held by many smokers are that negative mood increases smoking behavior and that this increase is due to the ability of smoking to alleviate negative affect. This study used a modified mood induction procedure to examine both the impact of smoking on induced mood, as well as the effect of induced mood on actual smoking behavior. Forty-eight smokers were randomly assigned to a smoking or a water-drinking comparison group. Each participant attended 3 sessions during which 1 of 3 mood states (positive, negative, or neutral) was induced. Contrary to expectation, smoking did not attenuate negative affect. However, negative mood induction subsequently quickened latency to smoke and increased number of puffs consumed ad lib.

Adult↗
PubMed2005

The influence of caffeine on nicotine's discriminative stimulus, subjective, and reinforcing effects.

Caffeine may acutely alter the discriminative stimulus and subjective effects of nicotine, perhaps explaining the association of coffee intake with smoking status. In this study, smokers were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0). Then, generalization of nicotine discrimination was tested, using both 2- and 3-choice ("novel" option) procedures, across a range of doses (0-20 microg/kg) following pretreatment with 0, 2.5, and 5.0 mg/kg caffeine p.o. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure. Caffeine pretreatment did not alter nicotine discrimination and self-administration. Caffeine and nicotine influenced some subjective and cardiovascular responses, but there were no interaction effects except for diastolic blood pressure. These results do not support the notion that caffeine acutely alters nicotine's discriminative stimulus, subjective, or reinforcing effects.

Administration, Intranasal↗
PubMed2005

The return to smoking: 1-year relapse trajectories among female smokers.

Research has demonstrated that a lapse in cigarette abstinence often leads smokers to fully relapse (i.e., return to daily smoking). However, patterns of smoking resumption beyond the point at which relapse occurs have not been examined in systematic follow-up studies. Daily cigarette intake data for 108 female adult smokers who participated in a smoking cessation trial were recorded at several points during the 365 days following the participants' quit date. SAS Proc Traj, a group-based mixture modeling procedure, was used to determine cigarette-use trajectories over time (i.e., patterns of smoking resumption). Over the 365 days, 27% of the sample maintained abstinence. Among the 73% who relapsed, four distinct trajectories emerged: low-level users (8% of the overall sample), moderate users (17%), slow-returners (15%), and quick-returners (33%). A few individual characteristics differentiated these groups. Overall, the findings illustrate that, after relapsing, smokers do not follow a unitary course of smoking resumption; rather, they exhibit more variable resumption patterns than previously assumed.

Adult↗
PubMed2005

The discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine as a function of light physical activity.

Smokers often experience the acute effects of cigarette smoking while they are engaged in the light physical activity of routine tasks. However, virtually all laboratory-based research on these effects is conducted under conditions of quiet rest and, thus, may not generalize to effects in the natural environment. We examined changes in the discriminative stimulus, subjective, cardiovascular, and reinforcing effects of nicotine in humans as a function of the level of concurrent physical activity. Men and women smokers (N = 17) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0 microg/kg) at rest. Three sessions then followed, in which the generalization of discrimination was tested across a range of doses (0-20 microg/kg) while at rest or engaged in very light or light physical activity (15% and 30% of heart rate reserve, respectively) via bicycle ergometer. Generalization testing involved both two- and three-choice ("novel" option) quantitative procedures. Self-reported mood via the Profile of Mood States and visual analog scales, and cardiovascular measures of heart rate and blood pressure were obtained concurrent with discrimination responding. Nicotine reinforcement was assessed after the end of generalization testing using a choice procedure under the same rest or activity conditions. Results showed that physical activity did not significantly alter nicotine discrimination or reinforcement, as no interactions between activity and nicotine were observed. When activity and nicotine influenced the same subjective and cardiovascular responses, they acted in a generally additive fashion. These findings suggest that research on the acute effects of nicotine conducted under typical resting laboratory conditions generally are not altered by light physical activity and so may generalize to the effects of nicotine under conditions common in the natural environment.

Administration, Intranasal↗
PubMed2004

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.

Adult↗
PubMed2004

Rate of nicotine onset from nicotine replacement therapy and acute responses in smokers.

The subjective and reinforcing effects of drugs of abuse may depend partly on their rate of onset, with faster acting formulations typically producing stronger effects than slower ones. In this within-subjects study, we examined the acute effects of nicotine replacement therapy via nicotine nasal spray (fast delivery) vs. transdermal nicotine patch (slow delivery) on craving, withdrawal, cardiovascular responses, subjective ratings, and reinforcing effects of smoking. Smokers (N=30) not seeking treatment participated in three sessions, each after overnight smoking abstinence, involving 14-mg nicotine (Nicoderm) or placebo patch, followed 4 hr later by intermittent administration of nicotine (Nicotrol) or placebo nasal spray. Specifically, the three group comparisons were nicotine patch condition (with placebo spray), nicotine spray condition (with placebo patch), and placebo condition (placebo spray and patch). Nicotine patch and nicotine spray were never administered in the same session. Blood nicotine levels were similar between nicotine patch and nicotine spray conditions, by design. Heart rate and systolic blood pressure were higher following nicotine spray vs. the other conditions, as hypothesized. However, other than reductions in craving related to nicotine spray and patch at some points, no differences between conditions were observed in withdrawal, subjective effects of sprays and smoking, or smoking reinforcement assessed by a computer task. Thus, under these acute conditions, the speed of nicotine delivery from nasal spray vs. patch differentially affected cardiovascular responses and perhaps craving but did not influence withdrawal, subjective ratings, and smoking reinforcement.

Administration, Cutaneous↗
PubMed2004

Instructions about nicotine dose influence acute responses to nasal spray.

Effects of substance use are typically assumed to be related to pharmacological actions. However, beliefs about the drug content of a substance may strongly influence subjective and reinforcing responses to that substance (i.e., "placebo" effects). We examined the subjective and reinforcing effects of a nasal spray containing no nicotine as a function of instructions about the nicotine content of the spray (Told Nicotine vs. Told No Nicotine). Smokers (n=49) not interested in quitting smoking abstained overnight prior to a single session in which they were randomly assigned to one of three groups, involving one of the two instructional sets or a group that got no spray. Following dose instructions, subjects in the two spray groups were administered one set of four sprays from the spray bottle and then rated them intermittently on items related to "reward" (e.g., "liking", amount they would pay for more) and other effects. At the same time points, they also rated mood, craving, and withdrawal, and had heart rate and blood pressure measured. Reinforcement was then determined by the number of ad libitum sprays they self-administered during a 20-min period. The no-spray group simply rested quietly during the session, while measures were assessed at the same time points as subjects in the other two groups. Those in the Told Nicotine group reported greater spray ratings of "how much nicotine," "liking," "satisfying," "buzz/head rush," and "similar to smoking" compared with the Told No Nicotine group. Craving decreased more for those Told Nicotine versus those Told No Nicotine, but also decreased more for those Told No Nicotine compared with the no spray group. There were no significant differences in amount they would pay for more sprays, withdrawal, mood, cardiovascular responses, or in spray self-administration. These results show that instructions about the nicotine content of a novel delivery device (nasal spray) can influence self-reported spray ratings and reduce craving but are limited with respect to effects on other measures of drug response.

Administration, Intranasal↗
PubMed2003

The subjective and reinforcing effects of visual and olfactory stimuli in alcohol drinking.

Nonpharmacological cues associated with drug intake may influence subjective and reinforcing effects of those drugs. Social drinkers (N = 80) participated in 2 sessions in which they rated and then consumed ad lib their preferred beer (with participants blind to brand). Visual and olfactory stimuli were obscured during 1 session (blocked) and not obscured during the other (unblocked). Dependent measures included ratings of "liking", "want another", and "desire to drink"; subjective mood; and ad lib beer consumption (reinforcement). Most ratings and ad lib consumption were lower during the blocked versus the unblocked condition. There were no interactions of blockade condition with sex and no effect of blockade on mood. These findings show that nonpharmacological stimuli associated with alcohol consumption influence alcohol's subjective and reinforcing effects.

Adult↗
PubMed2003

A history of depression and smoking cessation outcomes among women concerned about post-cessation weight gain.

Because a history of depression has been hypothesized to affect cessation efforts and may be particularly problematic for women concerned about weight gain, we sought to document the prevalence of depression history among weight-concerned women smokers and evaluate its effect on treatment outcome. We also evaluated the impact of baseline depressive symptoms and cessation-related changes in symptoms. Women (N = 219) were classified as depression history positive (Major Depressive Disorder [MDD]) (MDD+) or negative (MDD-) according to responses on the Inventory to Diagnose Depression-Lifetime Version. All women received a group-based smoking cessation treatment. Women provided expired-air carbon monoxide samples, completed measures of depressive symptoms, and were weighed at pretreatment and 1, 3, 6, and 12 months after quitting. Fifty-two per cent (n = 115) reported a lifetime history of major depressive disorder. Although MDD+ women were significantly more nicotine dependent, rates of continuous abstinence did not differ between MDD+ and MDD- women. However, MDD+ women were more likely to drop out of treatment prior to quitting. Additionally, depressive symptoms were associated with abstinence irrespective of depression history. Women who reported an increase in depressive symptoms from pre- to post-treatment were significantly less likely to be abstinent post-treatment, suggesting that depressive symptoms are more predictive of outcome than is previous disorder. Moreover, because of the prevalence of depression history among this subgroup of women smokers and its impact on early attrition, additional engagement and retention strategies may be useful.

Adult↗
PubMed2003

Common factors across acute subjective effects of nicotine.

Nicotine intake acutely induces many different subjective mood effects, which may be critical to understanding nicotine reinforcement. Some of these effects may cluster together, perhaps reflecting common underlying mechanisms (e.g., catecholamine release). In this study of 93 smokers, ex-smokers, and nonsmokers, we conducted factor analyses of responses to a battery of subjective measures (23 visual-analog scale items and Profile of Mood States [POMS] scales) following acute nicotine nasal spray administration. The goal was to identify homogeneous clusters among these diverse effects of nicotine. A subject's response to nicotine on each measure was determined by the slope of his or her dose-response curve (0, 10, 20 microg/kg nicotine). Results of factor analyses identified five factors, labeled "head rush" (head rush, buzzed, lightheaded, jittery), "positive affect" (comfortable, satisfied, relaxed, etc.), "negative affect" (anger, depression, tension), "fatigued" (tired, sedated, fatigue), and "energized" (stimulated, vigor). The factor structure was consistent between smoking status groups. However, as expected, groups differed on mean factor scores for head rush, positive affect, and energized, perhaps reflecting tolerance to these effects of nicotine. Although these specific findings require replication, they suggest that acute subjective responses to nicotine can be captured by a few common factors, potentially simplifying this assessment. Similar research may provide directions for exploring potential mechanisms responsible for these broad subjective effects of nicotine.

Administration, Intranasal↗