This review article focuses on the impact that the presence of pain has on drug self-administration in rodents, and the potential for using self-administration to study both addiction and pain, as well as their interaction. The literature on the effects of noxious input to the brain on both spinal and supraspinal neuronal activity is reviewed, as well as the evidence that human and rodent neurobiology is affected similarly by noxious stimulation. The convergence of peripheral input to somatosensory systems with limbic forebrain structures is briefly discussed in the context of how the activity of one system may influence activity within the other system. Finally, the literature on how pain influences drug-seeking behaviors in rodents is reviewed, with a final discussion of how these techniques might be able to contribute to the development of novel analgesic treatments that minimize addiction and tolerance.
Binge drinking is a public health concern due to its association with negative health outcomes as well as increased legal and social consequences. Previous studies have frequently used self-reported alcohol consumption to classify binge drinking episodes; however, these measures are often limited in both detail and accuracy. Some researchers have begun using additional measures such as blood (BAC) and breath (BrAC) alcohol concentrations to supplement self-report data. Transdermal alcohol testing, or the detection of alcohol expiration through the skin, offers advantages over BAC and BrAC measures by allowing for continuous and noninvasive monitoring of an individual's drinking behavior in real-time. Despite these advantages, this technology has not been widely used or studied outside of forensic applications. The present research compares transdermal alcohol concentration (TAC) and BrAC readings during the consumption of alcohol ranging from moderate drinking to binge drinking in 22 adult regular drinkers in order to investigate the sensitivity and specificity of the TAC monitors. We observed that BrAC and TAC measures were broadly consistent. Additionally, we were able to develop an equation that could predict BrAC results using TAC data, indicating TAC data would be an appropriate substitute in research and clinical contexts where BrAC readings are typically used. Finally, we were able to determine a cutoff point for peak TAC data that could reliably predict whether a participant had engaged in moderate or more than moderate drinking, suggesting TAC monitors could be used in settings where moderate or reduced drinking is the goal.
TRANSDERMAL ALCOHOL MONITORING; BINGE DRINKING; ALCOHOL ABUSE
Two common procedures for the treatment of missing information, listwise deletion and positive urine analysis (UA) imputation (e.g., if the participant fails to provide urine for analysis, then score the UA positive), may result in significant biases during the interpretation of treatment effects. To compare these approaches and to offer a possible alternative, these two procedures were compared to the multiple imputation (MI) procedure with publicly available data from a recent clinical trial. Listwise deletion, single imputation (i.e., positive UA imputation), and MI missing data procedures were used to comparatively examine the effect of two different buprenorphine/naloxone tapering schedules (7- or 28-days) for opioid addiction on the likelihood of a positive UA (Clinical Trial Network 0003; Ling et al., 2009). The listwise deletion of missing data resulted in a nonsignificant effect for the taper while the positive UA imputation procedure resulted in a significant effect, replicating the original findings by Ling et al. (2009). Although the MI procedure also resulted in a significant effect, the effect size was meaningfully smaller and the standard errors meaningfully larger when compared to the positive UA procedure. This study demonstrates that the researcher can obtain markedly different results depending on how the missing data are handled. Missing data theory suggests that listwise deletion and single imputation procedures should not be used to account for missing information, and that MI has advantages with respect to internal and external validity when the assumption of missing at random can be reasonably supported.
substance abuse treatment; missing data; positive drug test imputation; multiple imputation
Children's alcohol expectancies shift in late childhood/early adolescence in ways thought to lead to increased risk for adolescent alcohol use. The precise nature of this shift and the maturational processes that may influence it remain to be clarified. To these ends, we compared expectancy endorsement by grade across four expectancy domains: positive, negative, arousal and sedation, in a cross-sectional sample of 3rd-6th grade children attending afterschool programs (n = 299). Structural equation modeling (SEM) then was used to describe the relationships between expectancies and differences in: (a) cognitive ability and concept formation, (b) risk-taking personality traits, and (c) social exposure or values regarding alcohol-related information. Results showed those children in higher grades endorsed significantly more positive, negative and sedating expectancies for alcohol than their younger peers. Concept formation partially and fully mediated the relationships between grade and both positive and sedating expectancies, respectively, but not the relationship between grade and negative expectancies. Sensation seeking did not increase across grades in this sample, and the relationship between sensation seeking and positive expectancies was fully mediated by reported alcohol exposure and values. This study provides a basis for future exploration of developmental influences on alcohol expectancies, an understanding of which may be helpful in the design of prevention efforts targeting high risk youth prior to adolescence.
children; adolescent; sensation seeking; neurocognitive development; alcohol risk factors
The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n=40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as, greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations, suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD.
Alcohol abuse; posttraumatic stress disorder; comorbidity; cue reactivity; emotion; imagery
The association between smokers’ cue-induced craving and subsequent ability to initiate abstinence is unclear. Dependent smokers (N=158) completed a single cue-reactivity session prior to participating in a larger within-subjects study, which independently examined predictors of initiating quitting during 5 days each on nicotine versus placebo patch. In the larger study, all smokers used nicotine and placebo patch (double blind) for one week each following a preceding week of ad lib smoking, in a 2x2 cross-over design. Generalized estimating equation (GEE) models determined the predictive ability of cue-induced craving (cue reactivity) on subsequent success at initiating a quit attempt (at least 24hrs quit) for each patch condition. Smokers who exhibited greater craving during exposure to smoking cues had significantly greater odds of successfully initiating abstinence during either quit attempt week (i.e., the nicotine or placebo patch week). This relationship was not statistically significant for self-reported craving in response to neutral cues. However, a greater smoking-neutral cue difference score for cue-induced craving was also a significant predictor successfully initiating abstinence, but only among those not monetarily reinforced. Implications of these seemingly counterintuitive findings are discussed.
Predictors; Relapse; Cue reactivity; Abstinence initiation; Smoking cessation
Previous studies have reported that exercise decreases cocaine self-administration in rats with long-term access (8+ weeks) to activity wheels in the home cage. The purpose of this study was to (1) examine the importance of the temporal relationship between physical activity and initial drug exposure, (2) determine the effects of exercise on responding maintained by a nondrug reinforcer (i.e., food), and (3) investigate the effects of exercise on cocaine-induced increases in locomotor activity. To this end, female rats were obtained at weaning and divided into four groups: (1) EXE-SED rats were housed in exercise cages for six weeks and then transferred to sedentary cages after the first day of behavioral testing; (2) SED-EXE rats were housed in sedentary cages for six weeks and then transferred to exercise cages after the first day of behavioral testing; (3) SED-SED rats remained in sedentary cages for the duration of the study; and (4) EXE-EXE rats remained in exercise cages for the duration of the study. Relative to the sedentary group (SED-SED), exercise reduced cocaine self-administration in both groups with access to activity wheels after initial drug exposure (EXE-EXE, SED-EXE), but did not reduce cocaine self-administration in the group with access to activity wheels only before drug exposure (EXE-SED). Exercise also decreased the effects of cocaine on locomotor activity, but did not reduce responding maintained by food. These data suggest that exercise may reduce cocaine use in drug-experienced individuals with no prior history of aerobic activity without decreasing other types of positively reinforced behaviors.
cocaine; exercise; locomotor activity; physical activity; self-administration
Reactivity to smoking-related cues may play a role in the maintenance of smoking behavior and may change depending on smoking status. Whether smoking cue-related functional MRI (fMRI) reactivity differs between active smoking and extended smoking abstinence states currently is unknown.
We used fMRI to measure brain reactivity in response to smoking-related versus neutral images in 13 tobacco-dependent subjects prior to a smoking cessation attempt and again during extended smoking abstinence (52 ± 11 days) aided by nicotine replacement therapy.
Pre-quit smoking cue induced fMRI activity patterns paralleled those reported in prior smoking cue reactivity fMRI studies. Greater fMRI activity was detected during extended smoking abstinence than during the pre-quit assessment subcortically in the caudate nucleus and cortically in prefrontal (BA 6, 9, 44, 46), primary somatosensory (BA 1,2,3), temporal (BA 22, 41, 42), parietal (BA 7, 40) anterior cingulate (BA 24, 32), and posterior cingulate (BA 31) cortex.
These data suggest that during extended smoking abstinence, fMRI reactivity to smoking versus neutral stimuli persists in brain areas involved in attention, somatosensory processing, motor planning, and conditioned cue responding. In some brain regions, fMRI smoking cue reactivity is increased during extended smoking abstinence in comparison to the pre-quit state, which may contribute to persisting relapse vulnerability.
abstinence; addiction; caudate nucleus; fMRI; nicotine
A behavioral economic approach to understanding the relative value of alcohol may be useful for advancing medication development for alcoholism. Naltrexone is a heavily researched and moderately effective treatment for alcohol dependence making it a good candidate for a proof-of-concept study of behavioral economics and alcoholism pharmacotherapy.
This study examines naltrexone efficacy and pharmacogenetics in terms of the relative value of alcohol, assessed via demand curve analysis.
Materials and Methods
Participants were 35 heavy drinking (AUDIT ≥ 8) Asian Americans. A within-subjects cross-over medication design was used along with an intravenous alcohol challenge completed after four days of both naltrexone and placebo. At baseline and BrAC = 0.06 g/dl, participants completed an Alcohol Purchase Task, which assessed estimated alcohol consumption along escalating prices. Behavioral economic demand curve analysis yielded measures of Intensity, Elasticity, maximum expenditure (Omax), proportionate price insensitivity (Pmax) and breakpoint.
Compared to placebo, naltrexone significantly reduced Intensity, Omax and breakpoint. There were also a trend level medication effects on Pmax. BrAC was associated with increases in Pmax and breakpoint. A significant naltrexone × OPRM1 genotype interaction was observed for intensity of demand.
The present study extends the literature on naltrexone’s mechanisms through the application of a novel behavioral economic paradigm. These results indicate that naltrexone reduces several indices of demand for alcohol. This preliminary report provides further evidence for the effectiveness of naltrexone and supports the utility of a behavioral economic approach to alcoholism pharmacotherapy development.
Alcohol; Naltrexone; Behavioral Economics; Asian Americans
Current models of smoking and dependence assume a need to smoke at regular intervals to maintain nicotine levels, yet about 25% of adult smokers do not smoke daily. This subset of intermittent smokers (ITS) has gone largely unexamined. In this study, we describe the demographics, smoking history, and smoking behavior of ITS (n=282; 50.2% male) in comparison to daily smokers (DS; n=233; 60.7% male). Within ITS, we also compare “converted” ITS (CITS), who had previously smoked daily, with “native” ITS (NITS). On average, ITS were 34.66 years of age, and had smoked 42,850 cigarettes in the course of an average of 18 years of smoking. They smoked an average of 4.38 days per week, consuming 4.39 cigarettes a day on smoking days, and demonstrated considerable day-to-day variability in cigarette consumption. Almost half of ITS had Fagerstrom Test of Nicotine Dependence scores of 0, indicating no dependence. Compared to DS, ITS were more likely to cite alcohol drinking, socializing and being with other smokers as common contexts for smoking, and they also more often cited being angry or stressed. Data suggested that ITS’ behavior was not explained by use of other nicotine products or by economic constraints on smoking, nor by differences in psychological adjustment. Within ITS, CITS were heavier, more frequent, and more dependent smokers. In many respects, CITS were intermediate between NITS and DS. ITS show distinct patterns of smoking behavior that are not well explained by current models of nicotine dependence.
Smoking; dependence; non-daily smoking
Social learning theory considers self-efficacy as a causal factor in behavior change. However, in line with behavioral theory, recent clinical research suggests that self-efficacy ratings may reflect, rather than cause, behavior change. To test these two disparate views, self-efficacy was related to actual smoking abstinence on the next day (i.e. self-efficacy causes change), and abstinence status over one day was tested as a predictor of rated self-efficacy for being quit the next day (i.e. reflects change). All data were from two very similar cross-over studies evaluating the short-term effects of both placebo versus medication, nicotine patch (n=209) or varenicline (n=123), on smoking abstinence during week-long practice quit attempts. Placebo versus active medication periods were separated by an ad lib smoking washout, and analyses controlled for prior day's abstinence or self-efficacy values. Results were very consistent between studies in showing essentially bi-directional associations: daily self-efficacy predicted next day's abstinence, and current day's abstinence status predicted self-efficacy for not smoking the next day. However, secondary factors differentially predicted abstinence and, to a lesser extent, self-efficacy between these two medication studies. These data provide some support for both social learning and behavioral theories of smoking behavior change, although self-efficacy may only briefly predict subsequent short periods of abstinence as assessed in these studies. Nonetheless, because self-efficacy has long been assumed to cause behavior change, including smoking cessation, the notion of self-efficacy as a reflection of recent smoking behavior change in these studies warrants greater attention in clinical research on smoking cessation treatment.
smoking cessation; self-efficacy; smoking behavior; abstinence; nicotine dependence; behavior change
While extinction has been used as a treatment to reduce the power of drug cues, a better method is needed. Research with traditional reinforcers has shown that counterconditioning – pairing an appetitive cue with an aversive stimulus – can suppress cue-controlled behavior. The present experiment compared the counterconditioning and extinction of cocaine cues. Male rats were first trained to self-administer cocaine during a light cue. In the second phase, the light was paired with footshock in the Counterconditioning group. The Extincton group was treated similarly, except light presentations did not end in footshock. Counterconditioning suppressed cocaine seeking to a greater extent than extinction while the counterconditioning treatment was actively administered. On a subsequent stimulus compounding test where footshock was discontinued and the light was presented simultaneously with an untreated cocaine cue (a tone), suppressive effects of counterconditioning were evident during the early portion of the test, but not during later trials. Overall, results of the present experiment suggest that counterconditioning produces only temporarily suppressive effects on cue-controlled cocaine seeking. Methods for directly weakening the cue-drug association (e.g., “deepened extinction”) may prove to be more useful potential drug cue treatments.
This study examined the possibility that exposure to olfactory stimuli can reduce self-reported urge to smoke. After an initial assessment of self-reported urge, nicotine-deprived smokers evaluated the pleasantness of a series of 8 odors. Facial expressions during odor presentations were coded with P. Ekman and W. V. Friesen’s (1978a) Facial Action Coding System. After odor administration, participants were exposed to smoking cues. Next, participants were administered their most pleasant, least pleasant, or a control odor (water) and reported their urge to smoke. Results indicated that sniffing either a pleasant or unpleasant odor reduced reported urge to smoke relative to the control odor. Reported pleasantness of the odors did not differentially affect urge reduction. Odors eliciting negative-affect-related expressions, however, were less effective than odors that did not elicit negative-affect-related expressions in reducing reported urge. Results of this preliminary investigation provide support for the consideration of odor stimuli as an approach to craving reduction.
High trait hostility is associated with persistent cigarette smoking. To better understand mechanisms that may account for this association, we examined the effects of acute smoking abstinence and delayed versus immediate smoking reinstatement on responses to a social stressor among 48 low hostile (LH) and 48 high hostile (HH) smokers. Participants completed two laboratory sessions, one before which they had smoked ad lib and one before which they had abstained for the prior 12 hours. During each session, participants completed a stressful speaking task and then smoked immediately after the stressor or after a 15-minute delay. The effect of immediate vs. delayed smoking reinstatement on recovery in negative mood was significantly moderated by hostility. When reinstatement was delayed, HH participants showed significant increases in negative mood over time, whereas LH participants showed little change. When reinstatement was immediate, HH and LH smokers showed similar significant decreases in negative mood. Smoking abstinence did not moderate hostility effects. Cigarette smoking may prevent continuing increases in negative mood following social stress in HH smokers, which may partially explain their low rates of quitting.
smoking; hostility; social stress; personality; negative mood
There is a high degree of comorbidity between borderline personality disorder (BPD) and alcohol use disorders (AUDs) including alcohol abuse (AA) and dependence (AD). There is some evidence that this pattern of comorbidity may be associated with poorer prognosis. Although there are many different psychotherapeutic and pharmacological treatments for BPD and AUDs when they occur alone, there are very few treatment options when they occur together. The objective of this paper was to review the existing treatment options—both psychotherapeutic and pharmacological—for patients with dual diagnoses of BPD and AUDs and to explore alternative treatment options that warrant further study. There have been a number of studies that have examined the efficacy of specific psychotherapies targeting drinking among patients with comorbid BPD; however, their efficacy in reducing BPD symptoms is unknown. There are also three psychotherapies that were specifically developed for patients with BPD and SUDs, but only one of these (Dynamic Deconstructive Psychotherapy) has been tested among patients with dual diagnoses of BPD and AUDs. Research on pharmacotherapy for dual diagnoses of BPD and AUD is scarce, and no study has yet explored medication options that can concurrently manage symptoms of BPD and decrease alcohol consumption. Interestingly, there is growing evidence that anticonvulsants and second generation antipsychotics, the recent medications of choice for the management of anger in BPD, may also reduce alcohol craving and consumption. Although premature, these findings are encouraging especially for this population of patients for whom treatment options are very limited.
Borderline Personality Disorder; Alcohol Dependence; Comorbidity; Psychotherapy; Pharmacotherapy
Cocaine dependence is associated with neuroadaptations in stress and reward pathways that could alter stress and drug-related experiences and associated interoceptive sensations and result in enhanced craving states. Subjective interoceptive emotional and physiological responses experienced in stressful and drug cue situations were examined in abstinent cocaine-dependent individuals. Fifty-six treatment engaged cocaine-dependent patients with comorbid alcohol abuse or dependence were interviewed to identify personal stressful, drug cue, and neutral situations using a scene construction questionnaire (SCQ) that includes an emotional and physiological response checklist. Using this checklist, subjects identified emotional and bodily sensations that they recently experienced in the stress- and drug-related scenarios. Kappa coefficients indicated fair to moderate but significant degree of concordance in heart (p < .01), perspiration (p < .05), stomach (p < .05), and blood flow (p < .01) sensations for both stress and drug cue scenarios, while the McNemar change test indicated differential endorsement of interoceptive responses in stress and drug cue situations for breathing (p < .05), stomach (p < .05), tension (p < .05), and chest (p < .05) sensations, and for sad (p < .01), anger (p < .01), and excitement (p < .01) responses. Increased heartbeat and tension, tears, and anger urges were most commonly endorsed in the stress scenarios (between 50% and 79%), whereas butterflies in stomach, increased heartbeat and tension, jittery, restless, and warm excitement (53%–73%) were the most frequently endorsed sensations in the drug cue-related experiences. These self-reported sensations comprise both general arousal and specific interoceptive responses pertaining to stress or drug cue-related experiences in cocaine dependence, with potential value in guiding treatments targeting craving reduction.
cocaine dependence; stress and drug cues; interoceptive responses; drug craving
Naturally occurring impulsive choice has been found to positively predict alcohol consumption in rats. However, the extent to which experimental manipulation of impulsive choice may modify alcohol consumption remains unclear. In the present study, we sought to: (a) train low levels of impulsive choice in rats using early, prolonged exposure to reward delay, and (b) determine the effects of this manipulation on subsequent alcohol consumption. During a prolonged training regimen, three groups of male, adolescent Long-Evans rats (21-22 days old at intake) responded on a single lever for food rewards delivered after either a progressively increasing delay, a fixed delay, or no delay. Post-tests of impulsive choice were conducted, as was an evaluation of alcohol consumption using a limited-access, two-bottle test. Following delay-exposure training, both groups of delay-exposed rats made significantly fewer impulsive choices than did rats in the no-delay group. In addition, fixed-delay rats consumed significantly more alcohol during daily, 30-min sessions than no-delay rats. Possible mechanisms of these effects are discussed, as is the significance of these findings to nonhuman models of addiction.
impulsive choice; delay discounting; alcohol self-administration; lever press; rat
Topiramate, an anticonvulsant medication, is an efficacious treatment for alcohol dependence. To date, little is known about genetic moderators of side effects from topiramate. The objective of this study was to examine three single nucleotide polymorphisms (SNPs) of the glutamate receptor GluR5 gene (GRIK1) as predictors of topiramate-induced side effects in the context of a laboratory study of topiramate. Heavy drinkers (n = 51, 19 females), 75% of whom met criteria for an alcohol use disorder, completed a 5-week dose escalation schedule to a target dose of either 200 or 300 mg, or matched placebo. The combined medication groups were compared to placebo-treated individuals for side effects at target dose. Analyses revealed that a SNP in intron 9 of the GRIK1 gene (rs2832407) was associated with the severity of topiramate-induced side effects and with serum levels of topiramate. Genes underlying glutamatergic neurotransmission, such as the GRIK1 gene, may help predict heterogeneity in topiramate-induced side effects. Future studies in larger samples are needed to more fully establish these preliminary findings.
Ketamine is an NMDA receptor antagonist that is used in anesthetic, abuse, and therapeutic contexts. Recent evidence suggests that ketamine may affect not only glutamate systems, but may also act on receptors in the dopamine and serotonin systems. Because monoamine neurotransmitters play important trophic roles in prenatal development, we hypothesized that the behavioral consequences of prenatal exposure to ketamine may be moderated by genotype of the promoter in the monoamine oxidase-A (MAOA) gene. Eighty-two infant rhesus monkeys were identified that had known dates of conception and exposures to ketamine during gestation. Animals were tested at 3–4 months of age on a battery of tests assessing responsiveness to maternal separation, recognition memory, and contact with novel objects. Animals were classified by putative activity levels for the MAOA genotype. The effects of prenatal ketamine exposure were seen only in the context of MAOA genotype. Greater exposure to ketamine resulted in increased activity, less willingness to perform in the memory task, and reduced emotionality and novel object contact, but only for individuals with the low-activity genotype. Nearly all effects of exposure to ketamine were found in the first and second trimesters. MAOA genotype moderates the role of prenatal ketamine exposure at time points in gestation earlier than have been shown in past research, and are particularly evident for measures of emotionality. These results support the idea that the ketamine’s use might be best considered in light of individuals’ genetic characteristics.
ketamine; MAOA; temperament; anxiety; rhesus monkey
Pramipexole (PPX) is a dopamine agonist medication that has been implicated in the development of pathological gambling and other impulse control disorders. Johnson, Madden, Brewer, Pinkston, and Fowler (2011) reported that PPX increased male rats’ preference for gambling-like rewards (those arranged according to a variable-ratio schedule) over predictable rewards (those obtained from a fixed-ratio schedule). The present experiment explored the possibility that Johnson et al. underestimated the effects of PPX on gambling-like choices by constraining their rats’ daily income. In the present experiment conducted in a closed economy, PPX produced a dose-related increase in choice of the gambling-like alternative. In a control condition, PPX did not disrupt choice, suggesting the increased preference for gambling-like rewards was not due to nonspecific drug effects. Our findings are qualitatively consistent with those of Johnson et al., although the dose-related effect and larger effect size in the current study suggest that the effect of PPX on gambling-like choices is more pronounced when income was not constrained. This finding is consistent with clinical reports suggesting PPX is related to the development of problem gambling in humans.
pramipexole; dopamine agonist; gambling; Parkinson’s disease; rat
Delay discounting is the decline in a consequence's control of behavior as a function of its delay, and may be a fundamental behavioral process in drug dependence. Human delay-discounting studies have usually relied on choices between hypothetical rewards. Some human tasks have assessed delay discounting using operant procedures with consequences provided during the task, as in nonhuman animal studies. However, these tasks have limitations such as long duration, potentially indeterminate data, or confounding the effect of delay with probability. A study in 20 cocaine-dependent volunteers and 20 demographically matched non-cocaine-dependent volunteers was designed to investigate a novel operant delay-discounting task providing monetary reinforcement by coin delivery throughout the task (Quick Discounting Operant Task; QDOT). Participants completed a hypothetical delay-discounting procedure, a potentially real reward delay-discounting procedure, and an existing operant delay-discounting task: the Experiential Discounting Task (EDT). The QDOT resulted in complete data for all participants, showed systematic effects of delay that were well described by a hyperbolic function, had a maximum duration of 17 min, and resulted in relatively little variability in session earnings. QDOT performance was significantly, positively correlated with performance on the EDT but not the other tasks. The QDOT resulted in an effect size between the groups that was similar to most other delay discounting tasks examined, and showed the cocaine-dependent participants to delay discount significantly more than the control participants. The QDOT is an efficient operant human delay-discounting task that may be useful in a variety of experimental settings.
delay discounting; cocaine; real; hypothetical; human
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.
smoking; expectancies; placebo; nicotine; cognitive performance
Difficulty monitoring and inhibiting impulsive behaviors has been reported in marijuana (MJ) smokers; neuroimaging studies, which examined frontal systems in chronic MJ smokers, have reported alterations during inhibitory tasks. Diffusion tensor imaging (DTI) provides a quantitative estimate of white matter integrity at the microstructural level. We applied DTI, clinical ratings, and impulsivity measures to explore the hypotheses that chronic, heavy MJ smokers would demonstrate alterations in white matter microstructure and a different association between white matter measures and impulsivity relative to nonsmoking control subjects (NS). Fractional anisotropy (FA), a measure of directional coherence, and trace, a measure of overall diffusivity, were calculated for 6 locations including bilateral frontal regions in 15 chronic MJ smokers and 15 NS. Subjects completed clinical rating scales, including the Barratt Impulsivity Scale (BIS). Analyses revealed significant reductions in left frontal FA in MJ smokers relative to NS and significantly higher levels of trace in the right genu. MJ smokers also had significantly higher BIS total and motor subscale scores relative to NS, which were positively correlated with left frontal FA values. Finally, age of onset of MJ use was positively correlated with frontal FA values and inversely related to trace. These data represent the first report of significant alterations in frontal white matter tracts associated with measures of impulsivity in chronic MJ smokers. Early MJ use may result in reduced FA and increased diffusivity, which may be associated with increased impulsivity, and ultimately contribute to the initiation of MJ use or the inability to discontinue use.
diffusion tensor imaging; marijuana; impulsivity; white matter; age of onset
Studies examining the association between menstrual cycle phases and smoking behavior in women have yielded mixed results. The purpose of this study was to elucidate the associations between ovarian hormones and smoking by directly measuring ovarian hormone levels and obtaining a laboratory assessment of smoking behaviors. Four hypotheses were tested: increased smoking will be associated with 1) low absolute levels of estradiol and progesterone; 2) decreasing (i.e., dynamic changes in) estradiol and progesterone; 3) lower ratios of progesterone to estradiol, and 4) higher ratios of estradiol to progesterone. Female smokers (≥10 cigarettes/day) with regular menstrual cycles were recruited as part of a larger, ongoing study examining the influence of ovarian hormones on smoking cessation treatment. Participants completed two study visits, including a one-hour adlib smoking topography session, which provided a detailed assessment of smoking behavior. Both the change in hormone levels over time and the relative ratios of ovarian hormones were associated with smoking behavior, but each to a limited extent. Decreases in estradiol (r=−.21, p=.048), and decreases in progesterone (r=−.23, p=.03) were associated with increased puff intensity. Lower ratios of progesterone to estradiol were associated with a greater number of puffs (r=−.26, p=.01) and weight of cigarettes smoked (r=−.29, p=.005). The best predictors of smoking behavior were the ratio of progesterone to estradiol (z=−2.7, p=.004) and the change in estradiol and progesterone over time (z=−2.1, p=.02). This pattern of results may help to explain inconsistent findings in previous studies and suggest potential mechanisms by which hormones influence nicotine addiction.
Estrogen; progesterone; nicotine; tobacco; women