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
Polymorphisms of the µ-opioid receptor (OPRM1) and dopamine D4 receptor (DRD4) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions. This study examines these associations in the natural environment using ecological momentary assessment (EMA). Participants were non-treatment seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment. Data were culled from five consecutive days of drinking reports prior to medication randomization. Analyses revealed that, after drinking, carriers of the Asp40 allele of the OPRM1 gene reported higher overall levels of vigor and lower levels negative mood, as compared to homozygotes for the Asn40 variant. Carriers of the long allele (i.e., ≥ 7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRM1 and DRD4 VNTR genotypes appear to be alcohol dose-dependent. Specifically, carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated Blood Alcohol Concentration (eBAC) and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose, as compared to carriers of the major allele for each gene. Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode. This study extends findings on subjective intoxication, urge to drink, and their genetic bases from controlled laboratory to naturalistic settings.
OPRM1; DRD4; urge to drink; alcohol; EMA
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.
Higher levels of impulsivity have been implicated in the development of alcohol use disorders. Recent findings suggest that impulsivity is not a unitary construct, highlighted by the diverse ways in which the various measures of impulsivity relate to alcohol use outcomes. This study simultaneously tested the following dimensions of impulsivity as determinants of alcohol use and alcohol problems: risky decision-making, self-reported risk attitudes, response inhibition, and impulsive decision-making.
Participants were a community sample of non-treatment seeking problem drinkers (N = 158). Structural Equation Modeling (SEM) analyses employed behavioral measures of impulsive decision-making (Delay Discounting Task, DDT), response inhibition (Stop Signal Task, SST), and risky decision-making (Balloon Analogue Risk Task, BART), and a self-report measure of risk attitudes (Domain-specific Risk-attitude Scale, DOSPERT), as predictors of alcohol use and of alcohol-related problems in this sample.
The model fit well, accounting for 38% of the variance in alcohol problems, and identified two impulsivity dimensions that significantly loaded onto alcohol outcomes: (1) impulsive decision-making, indexed by the DDT; and (2) risky decision-making, measured by the BART.
The impulsive decision-making dimension of impulsivity, indexed by the DDT, was the strongest predictor of alcohol use and alcohol pathology in this sample of problem drinkers. Unexpectedly, a negative relationship was found between risky decision-making and alcohol problems. The results highlight the importance of considering the distinct facets of impulsivity in order to elucidate their individual and combined effects on alcohol use initiation, escalation, and dependence.
impulsivity; alcohol use; alcohol problems; delayed reward discounting; risk-taking
Cigarette purchase tasks (CPTs) are relatively new behavioral economic assessments that efficiently quantify motivation for tobacco by assessing how much an individual values cigarettes. This is achieved by assessing estimated cigarette consumption at escalating levels of price per cigarette and generating several measures of motivation from the resulting demand curve. The temporal stability of the indices generated from a CPT has not been examined to date and was the focus of the current study.
Participants were 11 moderately heavy smokers from the community who completed CPTs and other measures on 2 occasions 1 week apart. The CPT indices of the relative value of cigarettes were (a) intensity (i.e., consumption under minimal cost), (b) Omax (i.e., maximum expenditure for cigarettes), (c) breakpoint (i.e., first price suppressing consumption to 0), and (d) elasticity (i.e., proportionate price sensitivity).
Demand for cigarettes was initially insensitive to price changes (inelastic) but became increasingly sensitive (elastic) as prices increased. Correlations between the demand indices at both administrations were very high magnitude and statistically significant (rs = .76–.99, ps < .001), and no significant within-subjects differences were present.
These findings provide initial support for the temporal stability of motivation for tobacco as measured by a CPT. Future studies with larger samples and timeframes will be important to verify these findings.
Neuroeconomics integrates behavioral economics and cognitive neuroscience to understand the neurobiological basis for normative and maladaptive decision making. Delay discounting is a behavioral economic index of impulsivity that reflects capacity to delay gratification and has been consistently associated with nicotine dependence. This preliminary study used functional magnetic resonance imaging to examine delay discounting for money and cigarette rewards in 13 nicotine dependent adults. Significant differences between preferences for smaller immediate rewards and larger delayed rewards were evident in a number of regions of interest (ROIs), including the medial prefrontal cortex, anterior insular cortex, middle temporal gyrus, middle frontal gyrus, and cingulate gyrus. Significant differences between money and cigarette rewards were generally lateralized, with cigarette choices associated with left hemisphere activation and money choices associated with right hemisphere activation. Specific ROI differences included the posterior parietal cortex, medial and middle frontal gyrus, ventral striatum, temporoparietal cortex, and angular gyrus. Impulsivity as measured by behavioral choices was significantly associated with both individual ROIs and a combined ROI model. These findings provide initial evidence in support of applying a neuroeconomic approach to understanding nicotine dependence.
Nicotine dependence; smoking; tobacco; behavioral economics; neuroeconomics; delay discounting; impulsivity
The primary objectives of this study were to: (a) examine the neuroendocrine effects of naltrexone vs. placebo by comparing serum cortisol levels; and (b) test the biobehavioral correlates of naltrexone-induced changes in cortisol. Non-treatment seeking heavy drinkers (n = 37) completed two intravenous alcohol administrations, one after naltrexone (50 mg) and one after placebo. Cortisol levels were measured at baseline and after alcohol intake (BrAC = 0.06 g/dl) on both sessions, as were subjective responses to alcohol. Analyses revealed that naltrexone significantly raised overall cortisol levels compared to placebo. Cortisol levels decreased during alcohol administration and a stronger decrease was observed in the naltrexone condition. Cortisol levels were, in turn, inversely related to some of alcohol’s the reinforcing effects (i.e., alcohol ‘high,’ vigor) and positively associated with some of its unpleasant effects (i.e., sedation and subjective intoxication). These results suggest that naltrexone alters cortisol levels in heavy drinkers and that its effects on subjective responses to alcohol may be related, in part, to naltrexone’s ability to activate the HPA-axis.
naltrexone; alcohol; cortisol; HPA-axis; subjective intoxication
Behavioral economic alcohol purchase tasks (APTs) are self-report measures of alcohol demand that assess estimated consumption at escalating levels of price. However, the relationship between estimated performance for hypothetical outcomes and choices for actual outcomes has not been determined. The present study examined both the correspondence between choices for hypothetical and actual outcomes, and the correspondence between estimated alcohol consumption and actual drinking behavior. A collateral goal of the study was to examine the effects of alcohol cues on APT performance.
Forty one heavy-drinking adults (56% male) participated in a human laboratory protocol comprising APTs for hypothetical and actual alcohol and money, an alcohol cue reactivity paradigm, an alcohol self-administration period, and a recovery period.
Pearson correlations revealed very high correspondence between APT performance for hypothetical and actual alcohol (ps < .001). Estimated consumption on the APT was similarly strongly associated with actual consumption during the self-administration period (r = .87, p <.001). Exposure to alcohol cues significantly increased subjective craving and arousal, and had a trend-level effect on intensity of demand, in spite of notable ceiling effects. Associations among motivational indices were highly variable, suggesting multidimensionality.
These results suggest there may be close correspondence both between value preferences for hypothetical alcohol and actual alcohol, and between estimated consumption and actual consumption. Methodological considerations and priorities for future studies are discussed.
Alcohol; Behavioral Economics; Purchase Task; Demand; Craving; Cue Reactivity
Tobacco use disproportionately affects lower socioeconomic status (SES) groups. Current explanations as to why lower SES groups respond less robustly to tobacco control efforts and tobacco dependence treatment do not fully account for this disparity. The identification of factors that predict relapse in this population might help to clarify these differences. Good candidates for novel prognostic factors include the constellation of behaviors associated with executive function including self-control/impulsiveness, the propensity to delay reward, and consideration and planning of future events. This study examined the ability of several measures of executive function and other key clinical, psychological, and cognitive factors to predict abstinence for highly dependent lower SES participants enrolled in intensive cognitive-behavioral treatment for tobacco dependence. Consistent with predictions, increased discounting and impulsiveness, an external locus of control as well as greater levels of nicotine dependence, stress, and smoking for negative affect reduction predicted relapse. These findings suggest that these novel factors are clinically relevant in predicting treatment outcomes and suggest new targets for therapeutic assessment and treatment approaches.
Delayed reward discounting (DRD) is a behavioral economic index of impulsivity and numerous studies have examined DRD in relation to addictive behavior. To synthesize the findings across the literature, the current review is a meta-analysis of studies comparing DRD between criterion groups exhibiting addictive behavior and control groups.
The meta-analysis sought to characterize the overall patterns of findings, systematic variability by sample and study type, and possible small study (publication) bias.
Literature reviews identified 310 candidate articles from which 46 studies reporting 64 comparisons were identified (total N=56,013).
From the total comparisons identified, a small magnitude effect was evident (d=.15; p<.00001) with very high heterogeneity of effect size. Based on systematic observed differences, large studies assessing DRD with a small number of self-report items were removed and an analysis of 57 comparisons (n=3,329) using equivalent methods and exhibiting acceptable heterogeneity revealed a medium magnitude effect (d=.58; p<.00001). Further analyses revealed significantly larger effect sizes for studies using clinical samples (d=.61) compared with studies using nonclinical samples (d=.45). Indices of small study bias among the various comparisons suggested varying levels of influence by unpublished findings, ranging from minimal to moderate.
These results provide strong evidence of greater DRD in individuals exhibiting addictive behavior in general and particularly in individuals who meet criteria for an addictive disorder. Implications for the assessment of DRD and research priorities are discussed.
Delay discounting; Impulsivity; Addiction; Substance dependence; Alcohol; Tobacco; Nicotine; Stimulant; Opiate; Gambling; Meta-analysis
Behavioral economic demand for addictive substances is commonly assessed via purchase tasks that measure estimated drug consumption at a range of prices. Purchase tasks typically use escalating prices in sequential order, which may influence performance by providing explicit price reference points. This study investigated the consistency of value preferences on two alcohol purchase tasks that used either a randomized or sequential price order (price range: free to $30 per drink) in a sample of 91 young adult monthly drinkers. Randomization of prices significantly reduced relative response consistency (p < 0.01), although absolute consistency was high for both versions (>95%). Self-reported alcohol consumption across prices and indices of demand were highly similar across versions, although a few notable exceptions were found. These results suggest generally high consistency and overlapping performance between randomized and sequential price assessment. Implications for the behavioral economics literature and priorities for future research are discussed.
alcohol; purchase task; demand; behavioral economics; consistency
The prevalence of alcohol use disorders in college students necessitates that adequate measures exist to assess students for abuse and dependence. The Alcohol Dependence Scale (ADS) is a continuous measure of the severity of alcohol involvement found to have a unidimensional factor structure in clinical samples. The latent factor structure of the ADS in college drinkers has not been examined and this study sought to replicate unidimensionality. Heavy college drinkers (N=343) completed the ADS. Performance was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). The CFA did not support a single factor solution. Follow-up EFA revealed a two factor structure. The first, termed “Acute Excessive Drinking” consisted of relatively commonly endorsed items relating to loss of behavioral control, blackouts, and obsessive/compulsive drinking. The second, termed “Severe Withdrawal Symptoms,” consisted of relatively infrequently endorsed items relating to withdrawal symptoms. The ADS does not appear to have the same factor structure in college and clinical samples, making it inadvisable as a linear measure of alcohol problems within a college population.
Alcohol; Assessment; Factor Structure; College Students
High or inelastic demand for drugs is central to many laboratory and theoretical models of drug abuse, but it has not been widely measured with human substance abusers. The authors used a simulated cigarette purchase task to generate a demand curve measure of nicotine reinforcement in a sample of 138 adolescent smokers. Participants reported the number of cigarettes they would purchase and smoke in a hypothetical day across a range of prices, and their responses were well-described by a regression equation that has been used to construct demand curves in drug self-administration studies. Several demand curve measures were generated, including breakpoint, intensity, elasticity, Pmax, and Omax. Although simulated cigarette smoking was price sensitive, smoking levels were high (8+ cigarettes/day) at prices up to 50¢ per cigarette, and the majority of the sample reported that they would purchase at least 1 cigarette at prices as high as $2.50 per cigarette. Higher scores on the demand indices Omax (maximum cigarette purchase expenditure), intensity (reported smoking level when cigarettes were free), and breakpoint (the first price to completely suppress consumption), and lower elasticity (sensitivity of cigarette consumption to increases in cost), were associated with greater levels of naturalistic smoking and nicotine dependence. Greater demand intensity was associated with lower motivation to change smoking. These results provide initial support for the validity of a self-report cigarette purchase task as a measure of economic demand for nicotine with adolescent smokers.
tobacco; smoking; adolescents; behavioral economics; reinforcement; demand curve; nicotine dependence; motivation
Nicotine dependence continues to be a major public health problem worldwide and there is unequivocal evidence that genetics play a substantial role in its etiology. This review provides an overview of the evidence for genetic influences and recent advances in the field. Traditional quantitative genetics studies have revealed nicotine dependence is heritable and molecular genetics studies are providing increasing evidence that the genes responsible for nicotine’s pharmacokinetics and pharmacodynamics are particularly important. Despite considerable progress, a number of significant complexities and challenges remain. These include determining the specificity of genetic influences and clarifying the role of interactive contributions. One promising strategy for addressing these issues is an intermediate phenotype approach that attempts to identify the intervening proximal mechanisms that confer differential genetic risk. Understanding these mechanisms may permit more precision in understanding genetic influences and may also identify novel targets for intervention or prevention.
Nicotine Dependence; Genetics; Smoking; Tobacco; Intermediate Phenotype; Endophenotype
The present study sought to integrate convergent lines of research on the associations among the dopamine D4 receptor (DRD4) gene, novelty seeking, and drinking behaviors with the overall goal of elucidating genetic influences on problematic drinking in young adulthood. Specifically, this study tested a model in which novelty seeking mediated the relationship between DRD4 VNTR genotype and problematic alcohol use. Participants (N = 90, 40 females) were heavy drinking college students. Analyses using a Structural Equation-Modeling (SEM) framework suggested that the significant direct path between DRD4 VNTR genotype and problematic alcohol use was reduced to a trend level in the context of a model that included novelty seeking as a mediator, thereby suggesting that the effects of DRD4 VNTR genotype on problematic alcohol use among heavy drinking young adults were partially mediated by novelty seeking. Cross-group comparisons indicated that the relationships among the model variables were not significantly different in models for men versus women. These results extend recent findings of the association between this polymorphism of the DRD4 receptor gene, problematic alcohol use, and novelty seeking. These findings may also help elucidate the specific pathways of risk associated with genetic influences on alcohol use and abuse phenotypes.
alcohol; DRD4 VNTR; novelty seeking; genetics; mediation; structural equation modeling
The goal of this study was to examine the latent structure among measures of alcohol-induced subjective feelings of intoxication from a behavioral pharmacology perspective.
Data on subjective intoxication, measured concomitantly by the Subjective High Assessment Scale (SHAS), Biphasic Alcohol Effect Scale (BAES), and the Short-Version of the Profile of Mood States (POMS), were collected at three levels of breath alcohol concentration (BrAC) during an alcohol administration study in a sample of heavy drinkers (n = 135).
Results of exploratory factor analyses supported a three-factor model which captured the following dimensions of subjective intoxication: (a) stimulation and other pleasant effects; (b) sedative and unpleasant effects; and (c) alleviation of tension and negative mood. The tension-reduction factor was most consistently associated with more frequent drinking and alcohol problems in this sample.
These findings support the notion that the neuropharmacological and behavioral effects of alcohol are multifaceted and cannot be simply defined as either positive or negative. Rather, moderate levels of intoxication appear to have concomitant dimensions of positive reinforcement, negative reinforcement, and punishment. This study also suggests that factor scores may be useful in future alcohol administration studies in order to reduce the number of comparisons and perhaps increase statistical power to detect meaningful effects.
subjective intoxication; BAES; POMS; SHAS; factor analysis; alcohol
A behavioral economic approach to alcohol use disorders (AUDs) emphasizes both individual and environmental determinants of alcohol use. The current study examined individual differences in alcohol demand (i.e., motivation for alcohol under escalating conditions of price) and delayed reward discounting (i.e., preference for immediate small rewards compared to delayed larger rewards) in 61 heavy drinkers (62% with an AUD). In addition, based on theoretical accounts that emphasize the role of craving in reward valuation and preferences for immediate rewards, craving for alcohol was also examined in relation to these behavioral economic variables and the alcohol-related variables. Intensity of alcohol demand and delayed reward discounting were significantly associated with AUD symptoms, but not with quantitative measures of alcohol use, and were also moderately correlated with each other. Likewise, craving was significantly associated with AUD symptoms, but not with alcohol use, and was also significantly correlated with both intensity of demand and delayed reward discounting. These findings further emphasize the relevance of behavioral economic indices of motivation to alcohol use disorders and the potential importance of craving for alcohol in this relationship.
Alcohol; Behavioral Economics; Discounting; Demand; Craving
Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection), little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR) polymorphism in exon III of the human dopamine D4 receptor gene (DRD4) has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity.
We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+) report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a “one-night stand”) and report a more than 50% increase in instances of sexual infidelity.
DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism.
Delayed reward discounting (DRD) is a behavioral economic index of impulsivity that reflects the extent to which an individual devalues a reward based on its delay in time (i.e., preference for smaller immediate rewards relative to larger delayed rewards). Current smokers exhibit greater DRD compared to non-smokers, but also exhibit greater DRD compared to ex-smokers, suggesting that either DRD is inversely associated with successful smoking cessation or that smoking cessation itself reduces DRD. In a sample of treatment-seeking smokers (n = 57, 61% male, 85% Caucasian) participating in a randomized controlled smoking cessation trial, the current study prospectively examined DRD for money in general and at three magnitudes in relation to time to the participants’ first lapse to smoking. Survival analysis using Cox proportional-hazards regression revealed that DRD predicted days to first lapse (ps < .05-.01) and did so beyond nicotine dependence, sensation-seeking, and income in covariate analyses, with the exception of small magnitude discounting. In addition, dichotomous comparisons revealed significantly more impulsive baseline discounting for individuals who had lapsed by the two week and eight week follow-up visits. These findings indicate that high levels of DRD reflect a risk factor for poor smoking cessation treatment response. Interrelationships among the variables assessed and clinical strategies to improve outcomes for smokers who are high in DRD are discussed.
Nicotine Dependence; Treatment; Behavioral Economics; Delay Discounting; Impulsivity; Smoking Cessation
Although decision-making processes have become a principal target of study among addiction researchers, few studies have specifically examined decision making among individuals with alcohol dependence (AD) and findings to date are mixed. The present study examined the relationship between AD and decision-making, and tested whether different facets of antisocial and psychopathic traits explain this association.
Participants were men with AD (n = 22), AD and comorbid antisocial personality disorder (AD+ASPD; n = 17), or a history of recreational alcohol use, but no current or lifetime symptoms of a substance use disorder, conduct disorder, or ASPD (n = 21). Decision making was tested using the Iowa Gambling Task (IGT).
Across groups, participants reported similar levels of awareness of the contingencies of the task, but the AD groups with and without ASPD had poorer IGT performance compared to controls (p < .05). A block-by-block analysis revealed that while AD had slow, but steady improvement across the task, AD+ASPD exhibited initial improvement followed by a significant decrease in advantageous decision-making during the last 20 trials (p < .05). This was further confirmed via evidence that impulsive/antisocial personality traits, but not psychopathic traits, mediated poor IGT performance beyond ASPD diagnosis.
AD males favored risky choices regardless of whether they met criteria for ASPD. However, decision making deficits were more pronounced among those with ASPD, and personality traits characterized by impulsive and antisocial tendencies mediated the relationship between AD and decision-making.
Alcohol Dependence; Antisocial Personality Disorder; Psychopathy; Decision-Making
Behavioral economic demand curves are quantitative representations of the relationship between consumption of a drug and its cost. Demand curves provide a multidimensional assessment of reinforcement, but the relationships among the various indices of reinforcement have been largely unstudied.
The objective of the study is to use exploratory factor analysis to examine the underlying factor structure of the facets of alcohol reinforcement generated from an alcohol demand curve.
Materials and methods
Participants were 267 weekly drinkers [76% female; age M=20.11 (SD=.1.51); drinks/week M=14.33 (SD=11.82)] who underwent a single group assessment session. Alcohol demand curves were generated via an alcohol purchase task, which assessed consumption at 14 levels of prices from $0 to $9. Five facets of demand were generated from the measure [intensity, elasticity, Pmax (maximum inelastic price), Omax (maximum alcohol expenditure), and breakpoint], using both observed and derived calculations. Principal components analysis was used to examine the latent structure among the variables.
The results revealed a clear two-factor solution, which were interpreted as “Persistence,” reflecting sensitivity to escalating price, and “Amplitude,” reflecting the amount consumed and spent. The two factors were generally quantitatively distinct, although Omax loaded on both.
These findings suggest that alcohol reinforcement as measured via a demand curve is binary in nature, with separate dimensions of price-sensitivity and volumetric consumption. If supported, these findings may contribute theoretically and experimentally to a reinforcement-based approach to alcohol use and misuse.
Alcohol; Demand curve; Reinforcement; Exploratory factor analysis
Naltrexone (NTX) has proven to be effective with alcoholics in treatment, with most controlled clinical trials showing beneficial effects on heavy drinking rates. However, little is known about the behavioral mechanisms underlying the effects of NTX on drinking, or about patient characteristics that may moderate NTX's effects on drinking. In this study, ecological momentary assessment (EMA) techniques were used to investigate some of the putative mechanisms of naltrexone's effects on drinking in heavy drinkers who were not seeking treatment for alcohol problems. Polymorphisms in the D4 dopamine receptor (DRD4) gene and the μ-opiate receptor (OPRM1) gene, family history of alcohol problems, age of onset of alcoholism and gender were explored as potential moderators of NTX's effects.
After a one-week placebo lead-in period, heavy drinkers (n = 180), 63% of whom were alcohol-dependent, were randomized to 3 weeks of daily naltrexone (50 mg) or placebo. Throughout the study, participants used EMA on palm-pilot computers to enter, in real time, drink data, urge levels, and subjective effects of alcohol consumption.
NTX reduced percentage drinking days in all participants and reduced percent heavy drinking days in DRD4-L individuals; NTX decreased urge levels in participants with younger age of alcoholism onset; NTX increased time between drinks in participants who had more relatives with alcohol problems; and NTX reduced the stimulating effects of alcohol in women. OPRM1 status did not moderate any of NTX's effects.
These results confirm earlier findings of NTX's effects on drinking and related subjective effects, and extend them by describing individual difference variables that moderate these effects in the natural environment, using data collected in real time.
naltrexone; family history; genetics; treatment; pharmacology
Cue exposure treatment (CET) attempts to reduce the influence of conditioned substance cues on addictive behavior via prolonged cue exposure with response prevention (i.e., extinction), but has received only modest empirical support in clinical trials. This may be because extinction learning appears to be context dependent and a change in context may result in a return of conditioned responding (i.e., renewal), although this has received only limited empirical examination. The current study used a four-session laboratory analogue of CET to examine whether a change in context following three sessions of alcohol cue exposure with response prevention would result in renewal of conditioned responding. In addition, this study examined whether conducting extinction in multiple contexts would attenuate renewal of conditioned responding. In a one-way between-subjects design, 73 heavy drinkers (71% male) were randomized to three conditions: 1) single context extinction (extinction to alcohol cues in the same context for three sessions followed by a context shift at the fourth session); 2) multiple context extinction (extinction to alcohol cues in different contexts each day for all four sessions); and 3) pseudo-extinction control condition (exposure to neutral cues in the same context for three sessions followed by exposure to alcohol cues at the fourth session). The results revealed the predicted cue reactivity and extinction effects, but the hypotheses that a context shift would generate renewed cue reactivity and that multiple contexts would enhance extinction were not supported. Methodological aspects of the study and the need for parametric data on the context dependency of extinction to alcohol cues are discussed.
Alcohol; Cue Reactivity; Renewal; Conditioning; Craving; Translational Research
To achieve greater understanding of the brain mechanisms underlying nicotine craving in female smokers, we examined the influence of nicotine non-abstinence vs. acute nicotine abstinence on cue-elicited activation of the ventral striatum. Eight female smokers underwent an event-related functional magnetic resonance imaging (fMRI) paradigm presenting randomized sequences of smoking-related and non-smoking related pictures. Participants were asked to indicate by a key press the gender of individuals in smoking-related and non-smoking related pictures (gender discrimination task), to maintain and evaluate attention to the pictures. There was a significant effect of smoking condition on reaction times (RT) for a gender discrimination task intended to assess and maintain attention to the photographs—suggesting a deprivation effect of acute nicotine abstinence and a statistical trend indicating greater RTs for smoking cues than neutral cues. BOLD contrast (smoking vs. non-smoking cues) was greater in the non-abstinent vs. acutely abstinent conditions in the ventral striatum including the nucleus accumbens (VS/NAc). Moreover, a significant positive correlation was observed between baseline cigarette craving prior to scanning and VS/NAc activation (r=0.84, p=0.009), but only in the non-abstinent condition. These results may either be explained by ceiling effects of nicotine withdrawal in the abstinent condition or, may indicate reduced relative activation (smoking vs. neutral contrast) in the VS/NAc in the abstinent vs. non-abstinent conditions in this group of female smokers.
fMRI; Smoking; Tobacco; Cue reactivity; Ventral striatum; Nucleus accumbens
Season of birth (SOB) has been associated with many physiological and psychological traits including novelty seeking and sensation seeking. Similar traits have been associated with genetic polymorphisms in the dopamine system. SOB and dopamine receptor genetic polymorphisms may independently and interactively influence similar behaviors through their common effects on the dopaminergic system.
Based on a sample of 195 subjects, we examined whether SOB was associated with impulsivity, sensation seeking and reproductive behaviors. Additionally we examined potential interactions of dopamine receptor genes with SOB for the same set of traits. Phenotypes were evaluated using the Sociosexual Orientation Inventory, the Barratt Impulsivity Scale, the Eysenck Impulsivity Questionnaire, the Sensation Seeking Scale, and the Delay Discounting Task. Subjects were also asked about their age at first sex as well as their desired age at the birth of their first child. The dopamine gene polymorphisms examined were Dopamine Receptor D2 (DRD2) TaqI A and D4 (DRD4) 48 bp VNTR. Primary analyses included factorial gender×SOB ANOVAs or binary logistic regression models for each dependent trait. Secondary analysis extended the factorial models by also including DRD2 and DRD4 genotypes as independent variables. Winter-born males were more sensation seeking than non-winter born males. In factorial models including both genotype and season of birth as variables, two previously unobserved effects were discovered: (1) a SOB×DRD4 interaction effect on venturesomeness and (2) a DRD2×DRD4 interaction effect on sensation seeking.
These results are consistent with past findings that SOB is related to sensation seeking. Additionally, these results provide tentative support for the hypothesis that SOB modifies the behavioral expression of dopaminergic genetic polymorphism. These findings suggest that SOB should be included in future studies of risky behaviors and behavioral genetic studies of the dopamine system.