Cue-induced Craving Research Articles

Genetic predictors of cue- and stress-induced cigarette craving: an exploratory study.

Cigarette cravings in response to environmental cues and stressors are widely recognized as important predictors of smoking cessation outcomes. Accumulating evidence suggests that genetics plays a role in these craving responses, as well as in smoking cessation more generally. Previous studies of genetic polymorphisms have been limited by examination of single candidate genes and the use of broadly defined phenotypes (e.g., smoking history). In addition, research examining the similarities and differences between cue- and stress-induced cravings has been limited, although some evidence has suggested that they may have common genetic underpinnings. In the current study, we examined associations between a panel of 1,350 candidate genetic polymorphisms and craving responses to laboratory smoking cues and stressors. We hypothesized that common genetic polymorphisms would be predictive of both cue- and stress-induced craving. Nicotine-dependent smokers (n = 210) donated a blood sample, were exposed to neutral, smoking-related, and stress-related stimuli, and completed craving questionnaires immediately prior to and following each stimulus. Findings indicated that craving responses to smoking cues and stressors were moderately correlated (r = .44). However, genetic analysis revealed that cue and stress-induced cigarette craving were predicted by different polymorphisms, such that variants in the glycine and dopamine pathways were predictive of cue-induced craving, whereas variants in the stress-corticotropin pathway predicted stress-induced craving. Study results provide no support for the hypothesis that cue- and stress-induced craving have the same genetic predictors.

Psychometric Properties of the Autonomy over Tobacco Scale in German

Background/Aims: We investigated the psychometric properties of a German translation of the 12-item Autonomy over Tobacco Scale (AUTOS) among 1,195 eighth-grade students. Methods: Data for this study were collected as part of the fourth wave of data collection of the Smokefree Class Competition intervention in the Saxony-Anhalt region of Germany. Students from the control arm of the Smokefree Class Competition study who indicated that they had ever smoked ‘at least a few puffs’ on a cigarette were classified as ever-smokers. They self-completed questionnaires distributed by teachers. Results: AUTOS scores ranged from 0 to 36 with a distribution highly skewed toward lower-response categories. Inter-item correlations ranged from 0.65 to 0.89 (mean = 0.79, SD = 0.06). Composite reliability for the AUTOS was high (Ω = 0.96) and 3 lower-order factors were also reliable (withdrawal: 0.89, psychological dependence: 0.91, cue-induced cravings: 0.87). Concurrent validity was supported by strong relationships between the AUTOS and both lifetime cigarette consumption and current smoking frequency. Youths were 18 times more likely to be current smokers (95% CI = 11.9–27.2, p < 0.001) if they endorsed any AUTOS item. Conclusion: The German AUTOS is reliable and valid, and the results are consistent with the English AUTOS for use with adolescents.

Cue-induced craving and physiological reactions in recently and long-abstinent heroin-dependent patients

ObjectiveTo understand the different patterns of cue-induced craving and physiological reactions among recently abstinent and long-abstinent heroin-dependent patients. Method26 healthy adult controls (HC), 29 long-abstinent (more than 1year, LA), and 26 recently abstinent (less than 1month, RA) heroin-dependent individuals were exposed to heroin-related and neutral video cues, one video per session, on different days in random order. Self-reported heroin craving by a 10-point visual analog scale (VAS), physiological reactions [skin conductance (SC), muscle electromyography (MEG), skin temperature (TEMP)] and cardiovascular arousal [heart rates (HR), systolic blood pressure (HBP) and diastolic blood pressure (LBP)] were assessed at baseline and after exposure. ResultsBoth heroin-abstinent groups showed increased heroin craving, SC, MEG, HR, SBP and LBP after exposure to heroin-related video, compared to the control group and compared to exposure to the neutral video. Except the RA group showed more HR changes, changes of heroin craving, SC, MEG, HR, SBP and LBP after exposure to the heroin cue video were not different between the LA and RA groups. ConclusionsAbstinent heroin-dependent patients had elevated craving and physiological reactions after exposure to videos containing heroin-related cues and the cue induced responses still occurred in long-abstinent patients. This phenomenon should be addressed in treatment and recovery services for heroin dependence.

Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

BackgroundThe majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU).Methodology/Principal FindingsWe employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities.ConclusionsThese results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence.

Smoking and Neuroimaging: A Review

Cigarette smoking is a significant public health concern, often resulting in nicotine dependence, a chronic-relapsing psychiatric diagnosis that is responsible for up to 10% of the global cardiovascular disease burden. Due to its significantly deleterious effects on health, much research has been dedicated to elucidating the underlying neurobiology of smoking. This brief article is intended to provide a digestible synopsis of the considerable research being conducted on the underlying neural bases of cigarette smoking and nicotine dependence, especially for cardiologists who are often at the front lines of treating nicotine dependence. To this end, we first review some of the most common neuroimaging methodologies used in the study of smoking, as well as the most recent findings from this exciting area of research. Then, we focus on several fundamental topics including the acute pharmacological effects, acute neurocognitive effects, and the long-term neurobiological effects associated with smoking. We finally review recent findings regarding the neuropsychological processes associated with smoking cessation, including cue-induced craving and regulation of craving. Research in this field beginning to uncover how some of these neuropsychological processes are similar across clinical disorders which cardiologists also encounter frequently, such as craving for food resulting in overeating. We conclude with recommendations for future neuroimaging work on these topics.

Prazosin Effects on Stress‐ and Cue‐Induced Craving and Stress Response in Alcohol‐Dependent Individuals: Preliminary Findings

Stress, alcohol cues, and dysregulated stress responses increase alcohol craving and relapse susceptibility, but few pharmacologic agents are known to decrease stress- and cue-induced alcohol craving and associated stress dysregulation in humans. Here we report findings from a preliminary efficacy study of the alpha-1 receptor antagonist, prazosin, in modulating these relapse-relevant factors in alcohol-dependent individuals. Seventeen early abstinent, treatment-seeking alcohol-dependent individuals (12 men and 5 women) were randomly assigned to receive either placebo or 16 mg daily prazosin in a double-blind, placebo-controlled manner over 4 weeks. During week 4, all patients participated in a 3-day laboratory experiment involving 5-minute guided imagery exposure to stress, alcohol cue, and neutral-relaxing/control conditions, 1 exposure per day, on consecutive days in a random, counterbalanced order. Alcohol craving, anxiety, negative emotion, cardiovascular measures, and plasma hypothalamic-pituitary-adrenal (HPA; cortisol, adenocorticotropic hormone) were assessed repeatedly in each session. The prazosin group (n = 9) versus the placebo group (n = 8) showed significantly lower alcohol craving, anxiety, and negative emotion following stress exposure. The placebo group also showed significantly increased stress- and cue-induced alcohol craving, anxiety, negative emotion, and blood pressure (BP), as well as a blunted HPA response relative to the neutral condition, while the prazosin group showed no such increases in craving, anxiety, negative emotion, and BP, and no blunted HPA response to stress and alcohol cue exposure. Prazosin appears efficacious in decreasing stress- and cue-induced alcohol craving and may normalize the stress dysregulation associated with early recovery from alcoholism. Further research to assess the efficacy of prazosin in reducing alcohol craving and stress-related relapse risk is warranted.

Effects of Adrenal Sensitivity, Stress- and Cue-Induced Craving, and Anxiety on Subsequent Alcohol Relapse and Treatment Outcomes

Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes. Inpatient treatment in a community mental health center and hospital-based research unit. Treatment-engaged alcohol-dependent individuals and healthy controls. Time to alcohol relapse and to heavy drinking relapse. Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse. These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings suggest that new treatments that decrease adrenal sensitivity, stress- and cue-induced alcohol craving, and anxiety could be beneficial in improving alcohol relapse outcomes.

P01-91 - Pattern of craving response among smokers exposed to virtual reality

IntroductionTobacco craving is an intense desire to smoke. Cue-induced craving is considered the main responsible for relapse after smoking cessation. Cue Exposure Treatment (CET) consists of controlled and repeated exposure to stimuli associated with substance use in order to reduce craving associated.ObjectiveTo analyze the pattern of craving response of smokers exposed to Virtual Reality environments.MethodsForty-six smokers were exposed randomly to complex virtual scenes of 6 minutes long duration with smoking related cues that reproduce typical situations where people use to smokes. Craving was assessed before each exposure and 6 times during navigation with a visual analogic scale. For this secondary analysis the evolution of craving response were explored for the environments that produced the most and the least craving responses.ResultsIn the environment that produced the highest craving level, the pattern of response remains similar after the second assessment during the exposure, that is, after two minutes. For the environment that trigger the lowest levels, the responses gradually increased during the exposure and the highest level appeared in the last craving assessment, after 6 minutes.ConclusionsThis study has several implications. In the first place, virtual reality environments are able to elicit craving. In the second, we found that differents patterns of craving response exist in response to VR environments. Furthermore, the results obtained in the present study may be useful for cessation programs that include CET, in which is it necessary to know the pattern of desire during the exposure.

Commentary on Fidler et al. (2011): Identifying quitters who are at increased risk of relapse – where to from here?

In this issue, Fidler and colleagues compare the ability of two standard measures of dependence and a measure of urges to smoke during a normal smoking day, for their ability to predict successful cessation 1. Perhaps surprisingly, the authors report that the single-item measure of urge was the strongest predictor of short-term abstinence. With this finding, Fidler and colleagues have added to the list of indicators of relapse risk; a list that includes measures of nicotine dependence 2 and responsiveness to smoking-related cues (i.e. cue–reactivity 3), among others. Such measures are potentially clinically relevant: if health-care professionals are able to identify interested quitters who are going to have difficulty maintaining abstinence then they can successfully triage the smokers whom they see, focusing their efforts on the smokers who are most likely to have the greatest difficulty quitting. In health-care systems with limited resources—and we know of no other kind—the ability to focus resources on smokers in the most need is likely to be beneficial. The obvious next question, however, remains: once identified, how do we help these particularly vulnerable smokers to maximize their chances of success? Sadly, despite years of research into cessation treatments, we have made precious little progress on this front—relapse rates for first-line treatments remain unacceptability high 4. Without substantial improvements in the available treatment options there is limited practical use in our ability to identify those smokers who are at greater risk of failure. The finding that craving intensity experienced during ad libitum smoking predicts relapse risk concurs with previous findings that craving intensity experienced during a quit attempt predicts relapse risk 5-7. It is puzzling, however—in terms of our understanding of the underlying drivers of relapse—that treatments successful at attenuating craving are not more successful at helping smokers to quit. For example, we have reported that nicotine patches suppress background craving (along with many commonly reported withdrawal symptoms) experienced during a quit attempt, but that this effect does not account for the efficacy of patches 5. This discrepancy suggests that urge itself may not be a direct measure of relapse risk. It is possible, however, that self-reported urge is a marker for more proximal factors that relate to relapse risk. Fidler et al.'s measure of craving asked smokers to summarize craving retrospectively over a 24-hour period. While, on the face of it, this would seem to refer to ‘average’ craving over that time, it is likely that such recall in fact gives much greater weight to moments of intensive or ‘peak’ craving 8. This would probably reflect smokers' response to smoking cues, or susceptibility to cue-induced cravings, which we know are important in relapse 9, 10, and are not treated adequately with current regimes 9, 11. Gaining a better understanding of the nature of craving and response to smoking cues may suggest new, and hopefully more effective, treatment strategies. In conclusion, Fidler and colleagues' work provides evidence that a simple one-item measure of urge intensity can be used to successfully predict relapse risk, and suggests the need to explore further the dynamics of craving during ad libitum smoking. The development of effective treatments is necessary so that we can better assist interested quitters who are at a high risk of failure. Through their work at Pinney Associates, Drs Ferguson and Shiffman serve as consultants to GlaxoSmithKline Consumer Healthcare on an exclusive basis on matters relating to smoking cessation. Dr Shiffman also has an interest in a venture to develop a new nicotine replacement medication. Dr Bruno has nothing to disclose.

Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers

Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Randomized, double-blind, before-after controlled trial. Academic brain imaging center. Thirty nicotine-dependent smokers (paid volunteers). Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

Craving and treatment in smoking

Craving has been well known to be the most important clinical phenomenon in smoking cessation treatment and one that physicians always encounter. For successful and prolonged abstinence, understanding, evaluation, and management of craving are essential. The concept and definition of craving is still under debate, although its importance, relevance, and role in smoking relapse is evident. There are two types of craving, 'abstinence-induced craving' and 'cue-induced craving' according to time dynamic and causes. The evaluation of craving mainly depends on self-reported measures in the clinical field. Pharmacological treatments such as the nicotine patch, bupropion, and varenicline are effective for abstinence-induced craving. Psychosocial treatment and a few pharmacological agents such as nicotine gum and lozenges are useful for reducing cue-induced craving. This review was aimed at conveying up-to-date information on the characteristics, evaluation, and treatment of craving. Development of objective measurement tool for evaluation of craving is needed. The effects of pharmacological treatments on 'cue-induced craving' remain to be discovered. An active effort to alleviate each type of craving is necessary to enhance and prolong a patient's abstinence.

Cue-Reactors: Individual Differences in Cue-Induced Craving after Food or Smoking Abstinence

BackgroundPavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues?MethodsWe examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating.ResultsCertain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving.ConclusionsIn humans, like in nonhumans, there may be a “cue-reactive” phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation.

Stress-Induced and Cue-Induced Craving for Alcohol in Heavy Drinkers: Preliminary Evidence of Genetic Moderation by the OPRM1 and CRH-BP Genes

Neurobiological theories of addiction have highlighted disruption in stress pathways as a central feature of addictive disorders, and pharmacological treatments targeting stress mechanisms hold great promise. This study examines genetic determinants of stress-induced and cue-induced craving in heavy drinkers by testing single-nucleotide polymorphisms (SNPs) of the corticotrophin-releasing hormone binding protein (CRH-BP) gene and the mu-opioid receptor (OPRM1) gene. This study combines guided imagery stress exposure and in vivo alcohol cue exposure in a sample of 64 (23 women) non-treatment-seeking heavy drinkers. Analyses, uncorrected for multiple comparisons, revealed that a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample. The same SNP predicted greater affective responses to the stress manipulation, including greater levels of subjective tension and negative mood. The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. These initial results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes. Human laboratory models of stress and cue-induced craving may be useful in pharmacotherapy development targeting dysregulation of stress systems. Larger studies are needed to validate these preliminary findings, which should also be extended to clinical samples.

What is the significance of experiencing relaxation in response to the first use of nicotine?

Individuals who feel relaxed the first time they inhale from a cigarette are more likely to develop nicotine dependence. To determine if the relaxation response is associated only with specific aspects of dependence, a survey was administered to 1405 adolescents aged 14–18 years (mean 15.8 years) from four schools in Massachusetts. Nicotine dependence was measured with the Diagnostic and Statistical Manual (DSM-IV), and the loss of autonomy over tobacco was measured with the Hooked on Nicotine Checklist (HONC) and the Autonomy Over Smoking Scale. A feeling of relaxation was reported by 39.4% of 439 youth who had inhaled from a cigarette. Relaxation was associated with increased risk of current smoking (odds ratio (OR) = 5.7, p < 0.001), daily smoking (OR = 5.7, p < 0.001), a loss of autonomy on the HONC (OR = 5.0, p < 0.001), and a DSM-IV diagnosis (OR = 2.4, p < 0.02). In regression analyses, relaxation was not associated with psychological reliance on tobacco after controlling for nicotine withdrawal symptoms, and cue-induced craving. This study extends the literature by demonstrating that relaxation is associated with DSM-IV nicotine dependence, nicotine withdrawal, and aspects of cue-induced craving.

Development of a Measure of the Latency to Needing a Cigarette

People addicted to smoking experience a recurrent physiologic need to smoke anytime when they go too long without smoking. Our purpose was to evaluate the reliability and concurrent validity of a measure of the time elapsed between completion of smoking one cigarette and experiencing the need to smoke another (the latency to needing a cigarette-LTNC). We also investigated the relationship between the LTNC and dependence-related symptoms. An anonymous, self-administered survey was completed by 134 current adolescent smokers, and in a separate study, 32 smokers were asked to complete a retest. A frequent need to smoke was reported by 84.3% of the current smokers. Consistent with published case histories, the duration of the LTNC varied widely between the individuals. Among subjects who reported a regular need to smoke, 48% reported that their LTNC had shortened over time. The median LTNC among subjects who had smoked <100 cigarettes was 243 hours as compared with 2 hours for those who had smoked ≥ 100 cigarettes (p < .001). Test-retest reliability was reported to be excellent (r = .85, p < .001). As expected, LTNC correlated moderately and inversely with daily cigarette consumption (ρ = -.53, p < .001). It also correlated inversely with cue-induced craving (ρ = -.64, p < .001), psychological reliance on cigarettes (ρ = -.43, p < .001), nicotine withdrawal (ρ = -.57, p < .001), and pleasure obtained from smoking (ρ = -.39, p < .001). The data obtained in this study support the reliability and concurrent validity of the LTNC measure.

Determinants of Cue-Elicited Craving and Physiologic Reactivity in Methamphetamine-Dependent Subjects in the Laboratory

Objective: Craving for methamphetamine is commonly reported by heavy users of the drug and may increase the risk of relapse in newly abstinent individuals. Exposure to methamphetamine-associated cues in the laboratory can elicit measureable craving and autonomic reactivity in some individuals with methamphetamine dependence. In this study, clinical and demographic correlates of methamphetamine craving and the optimal conditions for its measurement in the laboratory are explored. Methods: Subjective (craving) and physiologic (heart rate and skin conductance) reactivity to presentation of methamphetamine-associated photo, video, and paraphernalia cues were evaluated in 43 subjects with methamphetamine dependence. Association of cue reactivity with demographic and clinical characteristics including duration, frequency, amount, and recency of methamphetamine use were assessed. Results: Craving was reported by fewer than half of subjects at baseline and by approximately 70% of subjects after methamphetamine cue exposure. Relative to baseline, subjective craving was increased by all three cue modalities to a similar extent. In general, physiological cue reactivity correlated poorly with cue-induced craving. Craving at baseline was strongly predictive of cue-induced craving. Differences in cue-induced craving were not associated with age, sex, education, employment, treatment status, or number of days using methamphetamine in the 60 days prior to study entry. In contrast, the degree of baseline craving was strongly associated with employment status and the number of days using methamphetamine in the past 60 days. Conclusions: Cue-induced craving for methamphetamine may be reliably measured in methamphetamine-dependent individuals in the laboratory. Further studies employing the cue reactivity paradigm in methamphetamine dependence are warranted.

Drug-related cue induced craving and the correlation between the activation in nucleus accumbens and drug craving: a fMRI study on heroin addicts

Objective To explore the neural mechanism underlying the craving of heroin addicts induced by picture-cue and the correlation between the brain activation degree in nucleus accumbens (NAc)/the ventral striatum and the scores of patients' self-report craving. Methods Twelve active heroin addicts and 12 matched healthy controls underwent fMRI scan while viewing drug-related pictures and neutral pictures presented in a block design paradigm after anatomical scanning in GE 3.0 T scanner. The fMRI data were analyzed with SPM 5. The change of craving scores was tested by Wilcoxon signed rank test. The Pearson correlation between the activation of NAc/the ventral striatum and the heroin craving score was tested by SPSS 13.0. Results The craving scores of heroin addicts ranged from 0 to 3.70(median 0.15) before exposed to drug cue and 0 to 5.10(median 3.25) after viewing drug-related pictures and showed statistical significance(Z = -2.666, P < 0.05). There were 16 activated brain areas when heroin dependent patients exposed to visual drug-related cue vs. neutral visual stimuli. The activation brain regions belonged to two parts, one was limbic system (amygdale, hippocampus, putamen, anterior cingulate cortex and caudate), another was brain cortex (middle frontal cortex, inferior frontal cortex, precentral gyrus, middle temporal cortex, inferior temporal cortex, fusiform gyrus, precuneus and middle occipital gyrus). The MR signal activation magnitude of heroin addicts ranged from 0.19 to 3.50. The result displayed a significant positive correlation between the cue-induced fMRI activation in NAc/the ventral striatum and heroin craving severity (r=0.829, P < 0.05). Conclusion Heroin shared the same neural circuitry in part with other drugs of abuse for cue-induced craving, including brain reward circuitry, visualspatial attention circuit and working memory region. In addition, the dysfunction of NAc/the ventral striatum may attribute to heroin-related cue induced craving. Key words: Heroin dependence; Corpus striatum; Magnetic resonance imaging

Current perspectives on selective dopamine D(3) receptor antagonists as pharmacotherapeutics for addictions and related disorders.

Repeated exposure to drugs of abuse produces long-term molecular and neurochemical changes that may explain the core features of addiction, such as the compulsive seeking and taking of the drug, as well as the risk of relapse. A growing number of new molecular and cellular targets of addictive drugs have been identified, and rapid advances are being made in relating those targets to specific behavioral phenotypes in animal models of addiction. In this context, the pattern of expression of the dopamine (DA) D(3) receptor in the rodent and human brain and changes in this pattern in response to drugs of abuse have contributed primarily to direct research efforts toward the development of selective DA D(3) receptor antagonists. Growing preclinical evidence indicates that these compounds may actually regulate the motivation to self-administer drugs and disrupt drug-associated cue-induced craving. This report will be divided into three parts. First, preclinical evidence in support of the efficacy of selective DA D(3) receptor antagonists in animal models of drug addiction will be reviewed. The effects of mixed DA D(2)/D(3) receptor antagonists will not be discussed here because most of these compounds have low selectivity at the D(3) versus D(2) receptor, and their efficacy profile is related primarily to functional antagonism at D(2) receptors and possibly interactions with other neurotransmitter systems. Second, major advances in medicinal chemistry for the identification and optimization of selective DA D(3) receptor antagonists and partial agonists will be analyzed. Third, translational research from preclinical efficacy studies to so-called proof-of-concept studies for drug addiction indications will be discussed.

An analysis on cue-induced craving and the related factors among heroin dependence

Objective To understand the cue-induced craving, physiological reactions to heroin-related cues, and to explore the factors that impact the cue-induced craving. Methods 369 abstinent heroin addicts were exposed to videotapes of heroin using and simulacrum after the self relaxation. The craving, abstinent symp-toms were measured before and after cue exposures. The physiological reactions were measured by multi-biofeed-back instrument before, during, and after cue exposure. BIS-Ⅱ questionnaire was used to collect information about their impulsive characteristic. Results After cue exposure, the self-reports scores of craving (t=11.24, P< 0.01), physiological index including heart rate((76.6±11.3) beats/min, F=19.23), skin conduct ((7.48± 4.25)μs, F=53.99), pupil size (t=11.73) had significant change in heroin addicts (P<0.01). Logistic regres-sion results showed that the scores of BIS-Ⅱ were related to cue-reduced craving (P=0.001,95% CI: 1.015～1. 065). Conclusions Exposure to drug-related cues can induces craving and physiological reactions in long term abstinence heroin addicts. High impulsive characteristic is a risk factor to induce drug-related craving. The inter-vention strategies should consider the impulsive characteristic and make a comprehensive intervention program to prevent relapse. Key words: Heroin dependence; Cue induce; Psycho-physiology indexDOI: 10.3760/cma.j.issn.1674-6554.2010.01.009

Counterconditioning reduces cue-induced craving and actual cue-elicited consumption.

Cue-induced craving is not easily reduced by an extinction or exposure procedure and may constitute an important route toward relapse in addictive behavior after treatment. In the present study, we investigated the effectiveness of counterconditioning as an alternative procedure to reduce cue-induced craving, in a nonclinical population. We found that a cue, initially paired with chocolate consumption, did not cease to elicit craving for chocolate after extinction (repeated presentation of the cue without chocolate consumption), but did so after counterconditioning (repeated pairing of the cue with consumption of a highly disliked liquid, Polysorbate 20). This effect persisted after 1 week. Counterconditioning moreover was more effective than extinction in disrupting reported expectancy to get to eat chocolate, and also appeared to be more effective in reducing actual cue-elicited chocolate consumption. These results suggest that counterconditioning may be more promising than cue exposure for the prevention of relapse in addictive behavior.